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Abstract Background With increasing incidence and treatment costs, chronic kidney disease (CKD) has become an important public health problem in China, especially in females. However, the genetic determinants are very limited. The estimated glomerular filtration rate (eGFR) based on creatinine is commonly used as a measure of renal function but can be easily affected by other factors. In contrast, eGFR based on both creatinine and cystatin C (eGFRcr-cys) improved the diagnostic accuracy of CKD. To our knowledge, no genome-wide association analysis of eGFRcr-cys has been conducted in the Chinese population. Methods By conducting a Genome-Wide association study(GWAS), a method used to identify associations between genetic regions (genomes) and traits/diseases, we examined the relationship between genetic factors and eGFRcr-cys in Chinese women, with 1983 participants and 3,838,121 variants included in the final analysis. Result One significant locus (20p11.21) was identified in the Chinese female population, which has been reported to be associated with eGFR based on cystatin C (eGFRcys) in the European population. More importantly, we found two new suggestive loci (1p31.1 and 11q24.2), which have not yet been reported. A total of three single nucleotide polymorphisms were identified as the most important variants in these regions, including rs2405367 (CST3), rs66588571(KRT8P21), and rs626995 (OR8B2). Conclusion We identified 3 loci 20p11.21, 1p31.1, and 11q24.2 to be significantly associated with eGFRcr-cys. These findings and subsequent functional analysis describe new biological clues related to renal function in Chinese women and provide new ideas for the diagnosis and treatment development of CKD.

Background Long noncoding RNA (lncRNA) and mRNA profiles in leukocytes have shown potential as biomarkers for acute ischemic stroke (AIS). This study aimed to identify altered lncRNA and target mRNA profiles in peripheral blood leukocytes as biomarkers and to assess the diagnostic value and association with AIS prognosis. Methods and Results Differentially expressed lncRNAs (DElncRNAs) and differentially expressed target mRNAs (DEmRNAs) were screened by RNA sequencing in the discovery set, which consisted of 10 patients with AIS and 20 controls. Validation sets consisted of a multicenter (311 AIS versus 303 controls) and a nested case–control study (351 AIS versus 352 controls). The discriminative value of DElncRNAs and DEmRNAs added to the traditional risk factors was estimated with the area under the curve. NAMPT‐AS, FARP1‐AS1, FTH1, and NAMPT were identified in the multicenter case–control study (P

Background: With the development of surgical techniques and medical equipment, the mortality rate of off-pump coronary artery bypass grafting (CABG) has been declining year by year, but there is a lack of convenient and accurate predictive models. This study aims to use two nomograms to predict 30-day mortality after off-pump CABG. Methods: Patients with isolated off-pump CABG from January 2016 to January 2021 were consecutively enrolled. Potential predictive factors were first screened by lasso regression, and then predictive models were constructed by multivariate logistic regression. To earlier identify high-risk patients, two nomograms were constructed for predicting mortality risk before and after surgery. Results: A total of 1840 patients met the inclusion and exclusion criteria. The 30-day mortality was 3.97 % (73/1840) in this cohort. Multivariate logistic analysis showed that age, BMI

Abstract Background Dyslipidemia and inflammation are significant factors for the onset of cardiovascular diseases (CVD); however, studies regarding their interactions on the risk of CVD are scarce. This study aimed to assess the interaction of dyslipidemia and high-sensitivity C-reactive protein (hs-CRP) on CVD. Methods This prospective cohort enrolled 4,128 adults at baseline in 2009 and followed them up until May 2022 for collecting CVD events. Cox-proportional hazard regression analysis estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of increased hs-CRP (≥ 1 mg/L) and dyslipidemia with CVD. The additive interactions were explored using the relative excess risk of interaction (RERI) and the multiplicative interactions were assessed with HRs (95% CI) while the multiplicative interactions were assessed by the HRs (95% CI) of interaction terms. Results The HRs of the association between increased hs-CRP and CVD were 1.42 (95% CI: 1.14–1.79) and 1.17 (95% CI: 0.89–1.53) among subjects with normal lipid levels and subjects with dyslipidemia, respectively. Stratified analyses by hs-CRP levels showed that among participants with normal hs-CRP ( 2.10 g/L had a significant association with CVD [HR (95% CI): 1.69 (1.14–2.51)]. Interaction analyses showed that increased hs-CRP had multiplicative and additive interactions with LDL-C ≥ 160 mg/dL and non-HDL-C ≥ 190 mg/dL on the risk of CVD [HRs (95%CIs): 0.309 (0.153–0.621), and 0.505 (0.295–0.866); RERIs (95%CIs): -1.704 (-3.430-0.021 and − 0.694 (-1.476-0.089), respectively, all P

BackgroundThrombospondin Type 1 Domain Containing Protein 1 (THSD1) has been suggested to be a new regulator of endothelial barrier function in the angiogenesis process, preserving vascular integrity. We sought to characterize the association of THSD1 genetic variants and mRNA expression with the risk of hemorrhagic stroke (HS) with population-based evidence.MethodsA case–control study was conducted with 843 HS cases and 1,400 healthy controls. A cohort study enrolled 4,080 participants free of stroke at baseline in 2009 and followed up to 2022. A synonymous variant, the main tag SNP rs3803264 of the THSD1 gene, was genotyped in all subjects, and peripheral leukocyte THSD1 mRNA expression was detected using RT-qPCR in 57 HS cases and 119 controls.ResultsIn the case–control study, rs3803264 AG/GG variations are associated with a decreased risk of HS with odd ratio (OR) and 95% confidence interval (CI) of the dominant model of 0.788 (0.648–0.958), p = 0.017. In addition, rs3803264 and dyslipidemia had a multiplicative interaction [OR (95% CI) = 1.389 (1.032, 1.869), p = 0.030]. In the cohort study, a similar association strength of rs3803264 dominant model and the risk of HS was observed with the incidence rate ratio (IRR) of 0.734 and p-value of 0.383. Furthermore, the risk of HS showed a non-linear as THSD1 mRNA expression increased (p for non-linearity

BackgroundThrombospondin-1 (THBS1) derived from platelets and acted as a critical mediator of hemostasis promoting platelet activation in thrombus formation. The biological connection of genetic variants and mRNA expression of THBS1 with ischemic stroke (IS) warrants further validation with population-based evidence.ObjectiveTo evaluate the association of single nucleotide polymorphisms (SNPs) and mRNA expression of THBS1 with the risks of IS and long-term death after stroke.MethodsA case-control study consisted of 4,584 IS patients recruited from five hospitals in Jiangsu, China, and 4,663 age-gender-matched controls free of IS. A cohort study enrolled 4,098 participants free of stroke and lasted from 2009 to 2022. Early collected 3158 IS patients aged between 35 and 80 years were followed up an average of 5.86-year to follow up their long-term death outcomes. Two tagSNPs of the THBS1 gene, rs2236471 and rs3743125, were genotyped in all subjects and THBS1 mRNA expression of peripheral leukocyte was measured using RT-qPCR in 314 IS cases and 314 controls.ResultsThere is no significant difference in genotype and haplotype frequencies of rs2236741 and rs3743125 between IS cases and controls (all P > 0.05). Furthermore, the cohort studies did not observe significant associations between THBS1 variants and the risk of IS incidence or long-term death after IS (all P > 0.05). The THBS1 mRNA expression level (2–ΔΔCT) in IS cases was approximately equal to that in controls (1.01 vs. 0.99, P = 0.833). In addition, THBS1 mRNA expression had no significant association with all-cause death, stroke death, and IS death of IS patients (all P > 0.05).ConclusionTherefore, our study suggested that there is no significant association of THBS1 polymorphisms and mRNA expression level with the risk of IS and long-term death after IS.

Advanced water injection has become an effective method for developing low-permeability reservoirs. However, after a period of high yield from fracturing, the injected water flows rapidly along high-capacity channels, which greatly reduces the sweep efficiency of reservoirs. In this work, the plugging process by microspheres and nanospheres from the fracture to the matrix was simulated through core experiments. The plugging performance of multi-scale microspheres (microspheres and nanospheres) on the core matrix was evaluated by measuring the plugging rate and other parameters. Enhanced oil recovery after synergistic plugging with multi-scale microspheres was used as the evaluation index, a sensitivity analysis of injection parameters was performed, and the best combination of injection parameters was optimized by orthogonal experiments. The experimental results showed that the plugging performance of nanospheres is mainly reflected in the filling of the core matrix, while the plugging performance of microspheres is mainly reflected by retention at the injection end of the core (as opposed to the fractured end face). The plugging rate of nanospheres reached 78.83%, which is much higher than the 30.28% rate achieved with microspheres. The maximum oil recovery after plugging was 19.12%, which corresponds to the following combination of injection parameters: total injection of 0.6 pore volume (PV), injection ratio between nanospheres and microspheres of 2:1, injection rate of 1.5 mL·min−1, and aging time of 6 days. Among the injection parameters, the injection ratio between nanospheres and microspheres had the greatest influence on the recovery of waterflooding after plugging, followed by the total injection of multi-scale microspheres. The injection rate and aging time had little effect.

Abstract The spontaneous imbibition (SI) process in shale oil reservoirs is not only influenced by capillary force, but also by the osmotic pressure between the fracturing fluid and formation water in the nanopores media. In this study, experimental methods are used to investigate the mechanisms of osmosis in the SI, taking into account the presence of initial formation water in shale oil reservoirs. To investigate the effect of osmosis, SI experiments were performed on the fine-grained felsic shale of the Qikou sag of Dagang oilfield. Low-field NMR testers and high-precision electronic balances are utilized for the measuring of oil–water migration. The results show that, when S w ≠ 0, high-salinity fluid SI can be divided into four stages: initial imbibition stage, drainage stage, secondary imbibition stage and stationary stage; when S w = 0, there is no drainage stage of high-salinity fluid SI; when S w ≠ 0 or S w = 0, low-salinity fluid SI can be called the “osmosis-enhanced SI”; and we have found that “newly formed pores or microfractures” as well as reducing salinity can promote SI. This article presents a systematic study of SI of shale oil reservoirs under the influence of osmosis, which provide useful information for reservoir numerical simulation and development program design.

Considering traditional continuously variable transmission cannot adapt to the working environment of high speed and high torque，an adder-type non-circular gear continuously variable transmission scheme without internal circulating torque is given. The torque characteristics and load conditions of non-circular gear teeth under relatively harsh working conditions are analyzed. General formulas for calculating the inertia moment，load moment and engine driving moment of this type of gear set are deduced，which provide a theoretical reference for optimal designs，production and processing of this type of continuously variable transmission.