Development and therapeutic implications of small molecular inhibitors that target calcium-related channels in tumor treatment.

Calcium ion dysregulation exerts profound effects on various physiological activities such as tumor proliferation, migration, and drug resistance. Calcium-related channels play a regulatory role in maintaining calcium ion homeostasis, with most channels being highly expressed in tumor cells. Additionally, these channels serve as potential drug targets for the development of antitumor medications. In this review, we first discuss the current research status of these pathways, examining how they modulate various tumor functions such as epithelial-mesenchymal transition (EMT), metabolism, and drug resistance. Simultaneously, we summarize the recent progress in the study of novel small-molecule drugs over the past 5 years and their current status.

Sliding Dynamics of a Small Charged Ring Chain on the Diblock Polyelectrolyte in Poly[2]catenane in the Presence of Counterions.

In this study, we investigate the sliding dynamics of small charged ring chains along the rigid central cyclic diblock polyelectrolyte of AnBn in radial charged poly[2]catenane in the presence of counterions using molecular dynamics simulations and the Lifson-Jackson formula, and our aim is to study the effects of electrostatical interaction strength, the size of the charged small ring chain, and the rigid block length of the diblock polyelectrolyte on the sliding dynamics of a small ring chain threaded on the rigid diblock polyelectrolyte. The mean-square displacement g3(t) of a small ring chain sliding along the rigid diblock polyelectrolyte of A10B10 exhibits oscillating behavior at short time scales for the moderate electrostatical interaction strength, while for the weak or strong electrostatic interactions, it is normal subdiffusion at short time scales. For n = 1, the diffusion coefficient D of the small ring chain sliding along the rigid diblock polyelectrolyte of A1B1 decreases monotonically as the relative electrostatic interaction strength A increases from A = 0.25-4. However, for n ≠ 1, the diffusion coefficient D of the small ring chain sliding along the rigid diblock polyelectrolyte of AnBn first decreases and then increases with the increase of A, and the nonmonotonous relationship between D and A becomes more obvious for larger n. In view of the free energy potential, the sliding diffusion of a small ring chain is governed by both the width of the free energy potential well and the height of the free energy potential barrier. According to the potential of mean force (PMF) of the small ring chain sliding along the rigid diblock polyelectrolyte, we find that our results are in good agreement with the theoretical analysis using the Lifson-Jackson formula. These results may help us to understand the diffusion motion of a ring chain in radial poly[n]catenanes from a fundamental point of view and control the sliding dynamics in molecular designs.

Dynamics of polymer chains confined to a periodic cylinder: molecular dynamics simulation vs. Lifson-Jackson formula.

The dynamics of polymer chains confined to a periodic cylinder is explored using molecular dynamics simulation and theoretical analysis. The cylinder is divided into two cavities in one periodicity: one cavity consists of a channel of length L1 and diameter D1 and another cavity is a channel of length L2 and diameter D2. For L1 = L2 = L/2, the diffusion coefficient D of a single confined polymer chain decreases rapidly with increase in periodicities L. For a fixed periodicity with L = L1 + L2 = constant, the diffusion coefficient D of a single confined polymer chain shows strong dependence on L1 (or L2). Moreover, for a multi-chain system with L1 = L2, the diffusion coefficient D shows strong non-monotonic dependence on the chain monomer density ρ, and the confined polymer chains diffuse fastest for ρ = 0.068, in which there are three polymer chains in two periodicities as well as two opposing effects: one is that the excluded volume effect between polymer chains can reduce the free energy barrier, and another is that when the chain monomer density ρ increases further, the entanglement effect increases, which leads to that the diffusion coefficient D decreases as ρ increases. Finally, we found that the diffusion coefficient D has a similar oscillation relationship with the ratio of R/L for different chain lengths N and different periodicity L, and the oscillation amplitude decreases gradually as R/L increases; here R is the mean end-to-end distance of a single confined polymer chain, i.e., . From the view of free energy potential, both the width of the free energy potential well and the height of the free energy potential barrier govern simultaneously the diffusion behavior of confined polymer chains. According to the mean force potential (PMF) based on the weighted histogram analysis method (WHAM), we found that our results agree very well with the theoretical analysis using the Lifson-Jackson formula. Our investigation may help us understand the dynamics of particles in a periodic medium, which is one of the interesting problems in many different fields of science, such as physics, chemistry and biology.

Pancreatic alpha cell glucagon-liver FGF21 axis regulates beta cell regeneration in a mouse model of type 2 diabetes.

AIMS/HYPOTHESIS: Glucagon receptor (GCGR) antagonism ameliorates hyperglycaemia and promotes beta cell regeneration in mouse models of type 2 diabetes. However, the underlying mechanisms remain unclear. The present study aimed to investigate the mechanism of beta cell regeneration induced by GCGR antagonism in mice. METHODS: The db/db mice and high-fat diet (HFD)+streptozotocin (STZ)-induced mice with type 2 diabetes were treated with antagonistic GCGR monoclonal antibody (mAb), and the metabolic variables and islet cell quantification were evaluated. Plasma cytokine array and liver RNA sequencing data were used to screen possible mediators, including fibroblast growth factor 21 (FGF21). ELISA, quantitative RT-PCR and western blot were applied to verify FGF21 change. Blockage of FGF21 signalling by FGF21-neutralising antibody (nAb) was used to clarify whether FGF21 was involved in the effects of GCGR mAb on the expression of beta cell identity-related genes under plasma-conditional culture and hepatocyte co-culture conditions. FGF21 nAb-treated db/db mice, systemic Fgf21-knockout (Fgf21-/-) diabetic mice and hepatocyte-specific Fgf21-knockout (Fgf21Hep-/-) diabetic mice were used to reveal the involvement of FGF21 in beta cell regeneration. A BrdU tracing study was used to analyse beta cell proliferation in diabetic mice treated with GCGR mAb. RESULTS: GCGR mAb treatment improved blood glucose control, and increased islet number (db/db 1.6±0.1 vs 0.8±0.1 per mm2, p<0.001; HFD+STZ 1.2±0.1 vs 0.5±0.1 per mm2, p<0.01) and area (db/db 2.5±0.2 vs 1.2±0.2%, p<0.001; HFD+STZ 1.0±0.1 vs 0.3±0.1%, p<0.01) in diabetic mice. The plasma cytokine array and liver RNA sequencing data showed that FGF21 levels in plasma and liver were upregulated by GCGR antagonism. The GCGR mAb induced upregulation of plasma FGF21 levels (db/db 661.5±40.0 vs 466.2±55.7 pg/ml, p<0.05; HFD+STZ 877.0±106.8 vs 445.5±54.0 pg/ml, p<0.05) and the liver levels of Fgf21 mRNA (db/db 3.2±0.5 vs 1.8±0.1, p<0.05; HFD+STZ 2.0±0.3 vs 1.0±0.2, p<0.05) and protein (db/db 2.0±0.2 vs 1.4±0.1, p<0.05; HFD+STZ 1.6±0.1 vs 1.0±0.1, p<0.01). Exposure to plasma or hepatocytes from the GCGR mAb-treated mice upregulated the mRNA levels of characteristic genes associated with beta cell identity in cultured mouse islets and a beta cell line, and blockage of FGF21 activity by an FGF21 nAb diminished this upregulation. Notably, the effects of increased beta cell number induced by GCGR mAb were attenuated in FGF21 nAb-treated db/db mice, Fgf21-/- diabetic mice and Fgf21Hep-/- diabetic mice. Moreover, GCGR mAb treatment enhanced beta cell proliferation in the two groups of diabetic mice, and this effect was weakened in Fgf21-/- and Fgf21Hep-/- mice. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that liver-derived FGF21 is involved in the GCGR antagonism-induced beta cell regeneration in a mouse model of type 2 diabetes.

SHP2 inhibition improves celastrol-induced growth suppression of colorectal cancer.

This study aimed to explore novel targets for celastrol sensitization in colorectal cancer (CRC) based on differentially regulated signals in response to high- or low-dose celastrol. Targeting signals were investigated using Western blotting or phosphorylated receptor tyrosine kinase (RTK) arrays. Corresponding inhibitors for the signals were individually combined with low-dose celastrol for the assessment of combined anti-CRC effects, based on proliferation, apoptosis, colony assays, and xenograft models. The potential mechanism for the combination of celastrol and SHP2 inhibition was further examined. Low-dose celastrol (<1 µM) did not effectively suppress AKT and ERK signals in CRC cells compared to high-dose celastrol (>1 µM). However, when combined with an AKT or ERK inhibitor, low-dose celastrol could cooperatively suppress CRC proliferation. Furthermore, failed AKT or ERK inhibition by low-dose celastrol may be due to reactivated RTK-SHP2 signaling with negative feedback. The combination of celastrol and the SHP2 inhibitor resulted in greatly reduced AKT and ERK signals, as well as greater inhibition of CRC growth than celastrol alone. Moreover, the mechanism underlying combination suppression was also involved in the activation of immune cell infiltration (mainly for CD8+ cells) in CRC tissues. Failure to inhibit RTK-SHP2-AKT/ERK signaling contributed to the lack of CRC growth suppression by low-dose celastrol. However, the combination of celastrol and the SHP2 inhibitor resulted in synergistic inhibition of CRC growth and provided a promising therapeutic target.

An Integrated Analysis of Lactation-Related miRNA and mRNA Expression Profiles in Donkey Mammary Glands.

Donkey milk is consumed by humans for its nutritional and therapeutic properties. MicroRNAs (miRNAs) and messenger RNAs (mRNAs) have been implicated in the regulation of milk component synthesis and mammary gland development. However, the regulatory profile of the miRNAs and mRNAs involved in lactation in donkeys is unclear. We performed mRNA-seq and miRNA-seq and constructed coexpression regulatory networks for the mammary glands during the lactating and nonlactating period of jennies. We identified 3144 differentially expressed (DE) mRNAs (987 upregulated mRNAs and 2157 downregulated mRNAs) and 293 DE miRNAs (231 upregulated miRNAs and 62 downregulated miRNAs) in the lactating group compared to the nonlactating group. The DE miRNA target mRNA were significantly associated with pathways related to RNA polymerase, glycosphingolipid biosynthesis, mRNA surveillance, ribosome biogenesis in eukaryotes, glycerophospholipid metabolism, Ras signaling, and the fly hippo signaling pathway. The mRNA-miRNA coregulation analysis showed that novel-m0032-3p, miR-195, miR-26-5p, miR-23-3p, miR-674-3p, and miR-874-3p are key miRNAs that target mRNAs involved in immunity and milk lipid, protein, and vitamin metabolism in the jenny mammary gland. Our results improve the current knowledge of the molecular mechanisms regulating bioactive milk component metabolism in the mammary glands and could be used to improve milk production in donkeys.

Quantitative analysis of the serum proteome during early pregnancy in mares.

Equine pregnancy is currently diagnosed by rectal palpation, ultrasonographic examination, or by measuring changes in hormones in the blood. In the present study, we identified proteins that are differentially expressed in the sera of early pregnant and non-pregnant mares in order to develop a novel method for diagnosing equine pregnancy. Serum samples were obtained from 18 adult mares, pregnancy at day 32 after ovulation (n = 9) and in diestrus (n = 9). Proteomic analysis of the samples was conducted using liquid chromatography-electrospray ionization-tandem mass spectrometry. We identified 467 proteins from a total of 3514 peptides. Thirty-two proteins (15 upregulated and 17 downregulated) were significantly differentially expressed between the two groups. The Gene Ontology enrichment analysis revealed that they are related to extracellular matrix assembly, blood coagulation, and hemostasis, and the prominent molecular functions were integrin binding, cell adhesion molecule binding, and glycine C-acetyltransferase activity. The pathway analysis of Kyoto Encyclopaedia of Genes and Genomes showed that the top three pathways identified were glycine, serine, and threonine metabolism; cysteine and methionine metabolism; and ether lipid metabolism. The selected five serum proteins were newly potential candidates for pregnancy diagnosis in mares.

High expression of SH2B adaptor protein 1 (SH2B1) indicates poor prognosis in colorectal cancer.

SH2B1, an adaptor protein associated with obesity, is closely related to the occurrence and development of a variety of tumors. To investigate the clinical significance of SH2B1 in colorectal cancer (CRC), expression of SH2B1 in colorectal normal tissues, adenomas, paracarcinoma tissues, carcinoma tissues, and metastatic tissues from 1003 CRC patients was detected by immunohistochemistry (IHC). The prediction power of SH2B1 for CRC prognosis was evaluated by Kaplan-Meier survival analysis and Cox regression model. Results revealed the expression of SH2B1 in carcinoma tissues was significantly higher than that in other tissues. High expression of SH2B1 was an independent risk factor for both disease-free survival (DFS) and disease-specific survival (DSS) and predicted unfavorable prognosis of CRC as well as poor chemotherapeutic response. Conclusively, SH2B1 can serve as an effective predictor for CRC survival and chemotherapeutic outcomes.

Sliding dynamics of multi-rings on a semiflexible polymer in poly[n]catenanes.

The sliding dynamics of one- or multi-ring structures along a semiflexible cyclic polymer in radial poly[n]catenanes is investigated using molecular dynamics simulations. The fixed and fluctuating (non-fixed) semiflexible central cyclic polymers are considered, respectively. With increasing bending energy of the central cyclic polymer, for the fixed case, the diffusion coefficient increases monotonically due to the reduction of the tortuous sliding path, while for the fluctuating case, the diffusion coefficient decreases. This indicates that the contribution of the polymer fluctuation is suppressed by a further increase in the stiffness of the central cyclic chain. Compared with the one ring case, the mean-square displacement of the multiple rings exhibits a unique sub-diffusive behavior at intermediate time scales due to the repulsion between two neighboring rings. In addition, for the multi-ring system, the whole set of rings exhibit relatively slower diffusion, but faster local dynamics of threading rings and rotational diffusion of the central cyclic polymer arise. These results may help us to understand the diffusion motion of rings in radial poly[n]catenanes from a fundamental point of view and control the sliding dynamics in molecular designs.

Sliding Dynamics of Ring Chains on Two Asymmetric/Symmetric Chains in a Simple Slide-Ring Gel.

The sliding dynamics along two asymmetric/symmetric axial chains of ring chains linked by a linear chainis investigated using molecular dynamics (MD) simulations. A novel sub-diffusion behavior is observed for ring chains sliding along eithera fixed rod-like chain or fluctuating axial chain on asymmetric/symmetric axial chainsat the intermediate time range due to their strongly interplay between two ring chains. However, two ring chains slide in the normal diffusion at along time range because their sliding dynamics can be regarded as an overall motion of two ring chains. For ring chains sliding on two symmetric/asymmetricaxial chains, the diffusion coefficient D of ring chains relies on the bending energy of axial chains (Kb) as well as the distance of two axial chains (d). There exists a maximum diffusion coefficient Dmax at d = d* in which ring chains slide at the fastest velocity due to the maximum conformational entropy for the linking chain between two ring chainsat d = d*. Ring chain slide on fixed rod-like axial chainsfaster in the symmetric axial chain case than that in the asymmetric axial chain case. However, ring chains slide on fluctuatingaxial chainsslower in the symmetric axial chain case than that in the asymmetric axial chain case. This investigation can provide insights into the effects of the linked chain conformation on the sliding dynamics of ring chains in a slide-ring gel.

Effects of Topological Constraints on Penetration Structures of Semi-Flexible Ring Polymers.

The effects of topological constraints on penetration structures of semi-flexible ring polymers in a melt are investigated using molecular dynamics simulations, considering simultaneously the effects of the chain stiffness. Three topology types of rings are considered: 01-knot (the unknotted), 31-knot and 61-knot ring polymers, respectively. With the improved algorithm to detect and quantify the inter-ring penetration (or inter-ring threading), the degree of ring threading does not increase monotonously with the chain stiffness, existing a peak value at the intermediate stiffness. It indicates that rings interpenetrate most at intermediate stiffness where there is a balance between coil expansion (favoring penetrations) and stiffness (inhibiting penetrations). Meanwhile, the inter-ring penetration would be suppressed with the knot complexity of the rings. The analysis of effective potential between the rings provides a better understanding for this non-monotonous behavior in inter-ring penetration.

An attraction-repulsion transition of force on two asymmetric wedges induced by active particles.

Effective interaction between two asymmetric wedges immersed in a two-dimensional active bath is investigated by computer simulations. The attraction-repulsion transition of effective force between two asymmetric wedges is subjected to the relative position of two wedges, the wedge-to-wedge distance, the active particle density, as well as the apex angle of two wedges. By exchanging the position of the two asymmetric wedges in an active bath, firstly a simple attraction-repulsion transition of effective force occurs, completely different from passive Brownian particles. Secondly the transition of effective force is symmetric for the long-range distance between two asymmetric wedges, while it is asymmetric for the short-range case. Our investigations may provide new possibilities to govern the motion and assembly of microscopic objects by taking advantage of the self-driven behaviour of active particles.

Association of sleep duration with stroke, myocardial infarction, and tumors in a Chinese population with metabolic syndrome: a retrospective study.

BACKGROUND: Previous studies have suggested that abnormal sleep duration is associated with increased risk of metabolic syndrome (MetS). However, evidence on the association of sleep duration with stroke, myocardial infarction (MI) and tumors in populations with MetS is limited. METHODS: A total of 8968 participants (2754 with MetS at baseline) were recruited in this retrospective study between March 2012 and December 2012. The baseline characteristics and information on sleep duration were collected by self-reported questionnaires. In addition, physical examination and blood test were also performed. The outcome events in this study were new onset of stroke, MI and tumors during subsequent follow-up. Multivariate logistic regressions were adopted to investigate the relationships between sleep duration and outcome events among different sleep duration groups (< 6 h, 6-7 h, 7-8 h [reference], 8-9 h, and > 9 h per day) in participants with MetS. RESULTS: The mean self-reported total sleep duration was 7.8 ± 1.2 h. Compared with participants with MetS slept for 7-8 h per day, the adjusted odds ratios (ORs) for those slept for > 9 h in stroke, MI and tumors were 2.014 (95% confidence interval [CI]: 1.184-3.426, P = 0.010), 1.731 (95% CI: 0.896-3.344, P = 0.102) and 2.159 (95% CI: 0.991-4.704, P = 0.053), respectively, whereas the adjusted ORs for those slept for < 6 h in stroke, MI and tumors were 2.249 (95% CI: 0.973-5.195, P = 0.058), 1.213 (95% CI, 0.358-4.104, P = 0.756) and 1.743 (95% CI, 0.396-7.668, P = 0.462), respectively. CONCLUSIONS: Long sleep duration (> 9 h) significantly increased the risk of stroke but not MI and tumors in individuals with MetS compared with 7-8 h of sleep duration. Short sleep duration (< 6 h) was not associated with the increased risk of stroke, MI and tumors in individuals with MetS.

Insulin resistance is associated with urinary albumin-creatinine ratio in normal weight individuals with hypertension and diabetes: The REACTION study.

BACKGROUND: The relationship between albuminuria and insulin resistance (IR) has not been clarified in previous studies. This study was conducted to examine whether IR is associated with albuminuria in subjects with diverse blood pressure and glycometabolism statuses. METHODS: This study included 34 136 participants whose data were drawn from a cross-sectional survey named the 2011 REACTION study. The participants were divided into six groups. The urinary albumin-creatinine ratio (UACR) and glomerular filtration rate (GFR) were used as markers of chronic kidney disease (CKD). Variance tests and logistic regression models were performed for homeostatic model assessment of insulin resistance (HOMA-IR) in relation to UACR and eGFR. RESULTS: First, UACR levels and HOMA-IR exhibited a positive correlation among participants (P < 0.05), and a negative correlation existed between GFR and HOMA-IR (P < 0.05). Second, in the hypertension with diabetes group, in individuals whose body mass index (BMI) was 18.5-24.0 kg/m2 , age was 50-60 years old, low density lipoprotein cholesterol (LDL-C) was 2.6-3.4 mmol/L or high density lipoprotein cholesterol (HDL-C) was 0.9-1.55 mmol/L, HOMA-IR was positively associated with UACR (P < 0.05). However, there was a negative correlation between GFR and HOMA-IR in the hypertension with diabetes group in individuals whose BMI was 18.5-24.0 kg/m2 or whose age was over 65 years old (P < 0.05). CONCLUSIONS: In the context of different blood pressure and glycometabolism statuses, the positive correlation between UACR levels and HOMA-IR was affected by BMI, age, LDL-C, HDL-C, and GFR. In patients with hypertension and diabetes, the early detection and intervention of IR and related risk factors in patients with normal BMI may reduce the occurrence of microalbuminuria and delay the progression of CKD.

Entropy-induced Separation of Binary Semiflexible Ring Polymer Mixtures in Spherical Confinement.

Coarse-grained molecular dynamics simulations are used to investigate the conformations of binary semiflexible ring polymers (SRPs) of two different lengths confined in a hard sphere. Segregated structures of SRPs in binary mixtures are strongly dependent upon the number density of system (ρ), the bending energy of long SRPs (Kb, long), and the chain length ratio of long to short SRPs (α). With a low ρ or a weak Kb, long at a small ratio α, long SRPs are immersed randomly in the matrix of short SRPs. As ρ and bending energy of long SRPs (Kb, long) are increased up to a certain value for a large ratio α, a nearly complete segregation between long and short SRPs is observed, which can be further characterized by the ratio of tangential and radial components of long SRPs velocity. These explicit segregated structures of the two components in spherical confinement are induced by a delicate competition between the entropic excluded volume (depletion) effects and bending contributions.

Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats.

BACKGROUND: Long-term diabetes-associated complications are the major causes of morbidity and mortality in individuals with diabetes. These diabetic complications are closely linked to immune system activation along with chronic, non-resolving inflammation, but therapies to directly reverse these complications are still not available. Our previous study demonstrated that mesenchymal stem cells (MSCs) attenuated chronic inflammation in type 2 diabetes mellitus (T2DM), resulting in improved insulin sensitivity and islet function. Therefore, we speculated that MSCs might exert anti-inflammatory effects and promote the reversal of diabetes-induced kidney, liver, lung, heart, and lens diseases in T2DM rats. METHODS: We induced a long-term T2DM complication rat model by using a combination of a low dose of streptozotocin (STZ) with a high-fat diet (HFD) for 32 weeks. Adipose-derived mesenchymal stem cells (ADSCs) were systemically administered once a week for 24 weeks. Then, we investigated the role of ADSCs in modulating the progress of long-term diabetic complications. RESULTS: Multiple infusions of ADSCs attenuated chronic kidney disease (CKD), nonalcoholic steatohepatitis (NASH), lung fibrosis, and cataracts; improved cardiac function; and lowered serum lipid levels in T2DM rats. Moreover, the levels of inflammatory cytokines in the serum of each animal group revealed that ADSC infusions were able to not only inhibit pro-inflammatory cytokines IL-6, IL-1ß, and TNF-α expression but also increase anti-inflammatory cytokine IL-10 systematically. Additionally, MSCs reduced the number of iNOS(+) M1 macrophages and restored the number of CD163(+) M2 macrophages. CONCLUSIONS: Multiple intravenous infusions of ADSCs produced significant protective effects against long-term T2DM complications by alleviating inflammation and promoting tissue repair. The present study suggests ADSCs may be a novel, alternative cell therapy for long-term diabetic complications.

Filter-Free Selective Light Monitoring by Organic Field-Effect Transistor Memories with a Tunable Blend Charge-Trapping Layer.

Integration of selective photodetection and signal storage in a single device, such as organic field-effect transistor (OFET) memories, meets the demands for radiation monitoring and protection. A new strategy is developed to achieve filter-free and selective light monitoring by adopting a solution-processed blend charge-trapping layer in OFET memories, where the charge-trapping layer is composed of phenyl-C61-butyric acid methyl ester (PCBM) dispersed in a polymer electret thin film. The OFET memory without PCBM shows response only to ultraviolet light, whereas the spectral response edges are extended to the visible and near-infrared regions in the corresponding devices with relatively low and high contents of PCBM in the charge-trapping layer, respectively. A set of OFET memories with different PCBM contents is used to qualitatively evaluate the light composition in an optical source. The tunable spectral response in the OFET memories is ascribed to the additional photoassisted charge-trapping paths depending on the blend ratio in the charge-trapping layer. This mechanism may inspire alternative approaches to organic-based optical sensing and monitoring in flexible and wearable electronics.

The Association between Resting Heart Rate and Urinary Albumin/Creatinine Ratio in Middle-Aged and Elderly Chinese Population: A Cross-Sectional Study.

OBJECTIVE: In general population, resting heart rate (RHR) is associated with cardiovascular disease. However, its relation to chronic kidney disease (CKD) is debated. We therefore investigated the relationship between RHR and urinary albumin/creatinine ratio (UACR, an indicator of early kidney injury) in general population at different levels of blood pressure and blood glucose. METHODS: We screened out 32,885 subjects from the REACTION study after excluding the subjects with primary kidney disease, heart disease, tumor history, related drug application, and important data loss. The whole group was divided into four groups (Q1: RHR ≤ 71, Q2: 72 ≤ RHR ≤ 78, Q3: 79 ≤ RHR ≤ 86, and Q4: 87 ≤ RHR) according to the quartile of average resting heart rate. The renal function was evaluated by UACR (divided by quartiles of all data in the center to which the subject belonged). Ordinary logistic regression was carried out to explore the association between RHR and UACR at diverse blood pressure and blood glucose levels. RESULTS: The subjects with higher RHR quartile tend to have a higher UACR, even multifactors were adjusted. After stratifying the subjects according to blood pressure and blood glucose, the positive relationship between RHR and UACR remained in the subjects with normal blood pressure and normal glucose tolerance, while in the hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) group and the diabetic mellitus (FPG ≥ 7.0 mmol/L and/or PPG ≥ 11.1 mmol/L) group, the relationship disappeared. In the subjects without hypertension, compared with the Q1 group, the UACR is significant higher in the Q3 group (OR: 1.11) and the Q4 group (OR: 1.22). In the subjects with normal glucose tolerance (NGT), compared with the Q1 group, the UACR is significantly higher in the Q3 group (OR: 1.13) and the Q4 group (OR: 1.19). CONCLUSIONS: The population with higher RHR tend to have a higher UACR in the normal blood pressure group and the normal glucose tolerance group.

Self-reported sleep duration and daytime napping are associated with renal hyperfiltration and microalbuminuria in an apparently healthy Chinese population.

BACKGROUND: Sleep duration affects health in various ways. The objective of the present study was to investigate the relationships among sleep duration, daytime napping and kidney function in a middle-aged apparently healthy Chinese population. METHODS: According to self-reported total sleep and daytime napping durations, 33,850 participants who were 38-90 years old and recruited from eight regional centers were divided into subgroups. Height, weight, waist circumference, hip circumference, blood pressure, biochemical indexes, fasting blood glucose (FBG), postprandial blood glucose (PBG), HbA1c, creatinine and urinary albumin-creatinine ratio (UACR) were measured and recorded for each subject. Microalbuminuria was defined as UACR ≥30 mg/g, chronic kidney disease (CKD) was defined as eGFR <60 ml/min, and hyperfiltration was defined as eGFR ≥135 ml/min. Multiple logistic regression was applied to investigate the association between sleep and kidney function. RESULTS: Compared to sleeping for 7-8 h/day, the ORs for microalbuminuria for sleeping for >9 h/day, 8-9 h/day 6-7 h/day and <6 h/day were 1.343 (1.228-1.470, P<0.001), 1.223 (1.134-1.320, P<0.001), 1.130 (1.003-1.273, P = 0.045) and 1.140 (0.908-1.431, P = 0.259), respectively. The eGFR levels exhibited a U-shaped association with sleep duration among subjects with an eGFR ≥90 ml/min and an N-shaped association with sleep duration among subjects with an eGFR <90 ml/min. The OR for hyperfiltration for >9 h/day of sleep was 1.400 (1.123-1.745, P = 0.003) among participants with an eGFR ≥90 ml/min. Daytime napping had a negative effect on renal health. Compared to the absence of a napping habit, the ORs for microalbuminuria for 0-1 h/day, 1-1.5 h/day and >1.5 h/day of daytime napping were 1.552 (1.444-1.668, P<0.001), 1.301 (1.135-1.491, P<0.001) and 1.567 (1.353-1.814, P<0.001), respectively. CONCLUSION: The association of total sleep duration with renal health outcomes is U-shaped. Daytime napping has a negative effect on renal health.