The Therapeutic Effects of Baicalein on the Hepatopulmonary Syndrome in the Rat Model of Chronic Common Bile Duct Ligation.

Background and Aims: Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease. To date, liver transplantation remains the only effective treatment for HPS. This study aimed to explore the preventative role of baicalein in HPS development. Methods: Sixty male rats were randomly assigned to three groups: sham, common bile duct ligation (CBDL), and baicalein, receiving intraperitoneal injections of baicalein (40 mg·kg-1·d-1, diluted in saline) for 21 days. Survival rate, liver and kidney function, and bile acid metabolism levels were evaluated. Liver and lung angiogenesis and hepatic glycogen staining were assessed, and the expression of relevant proteins was evaluated by immunohistochemistry. Results: Baicalein improved survival rates and hypoxemia in rats post-CBDL, reducing angiogenic protein levels and enhancing glucose homeostasis. Compared to the untreated group, baicalein suppressed the expression of vascular endothelial growth factor, placental growth factors, matrix metalloprotease 9 and C-X-C motif chemokine 2, and it increased the expression of glycemic regulatory proteins, including dipeptidyl peptidase-4, sirtuin 1, peroxisome proliferator-activated receptor gamma co-activator 1α, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3. Conclusion: Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs, showing promise as a treatment for HPS.

Elevated circulating BMP9 aggravates pulmonary angiogenesis in hepatopulmonary syndrome rats through ALK1-Endoglin-Smad1/5/9 signalling.

BACKGROUND: Bone morphogenetic protein 9 (BMP9) is a hepatokine that plays a pivotal role in the progression of liver diseases. Moreover, an increasing number of studies have shown that BMP9 is associated with hepatopulmonary syndrome (HPS), but its role in HPS is unclear. Here, we evaluated the influence of CBDL on BMP9 expression and investigated potential mechanisms of BMP9 signalling in HPS. METHODS: We profiled the circulating BMP9 levels in common bile duct ligation-induced HPS rat model, and then investigated the effects and mechanisms of HPS rat serum on pulmonary vascular endothelial dysfunction in rat model, as well as in primarily cultured rat pulmonary microvascular endothelial cells. RESULTS: Our data revealed that circulating BMP9 levels were significantly increased in the HPS rats compared to control group. Besides, the elevated BMP9 in HPS rat serum was not only crucial for promoting endothelial cell proliferation and tube formation through the activin receptor-like kinase1 (ALK1)-Endoglin-Smad1/5/9 pathway, but also important for accumulation of monocytes. Treatments with ALK1-Fc or silencing ALK1 expression to inhibit the BMP9 signalling pathway effectively eliminated these effects. In agreement with these observations, increased circulating BMP9 was associated with an increase in lung vessel density and accumulation of pro-angiogenic monocytes in the microvasculature in HPS rats. CONCLUSIONS: This study provided evidence that elevated circulating BMP9, secreted from the liver, promote pulmonary angiogenesis in HPS rats via ALK1-Endoglin-Smad1/5/9 pathway. In addition, BMP9-regulated pathways are also involved in accumulation of pro-angiogenic monocytes in the pulmonary microvasculature in HPS rats.

Amber rainbow ribbon effect in broadband optical metamaterials.

Using the trapped rainbow effect to slow down or even stop light has been widely studied. However, high loss and energy leakage severely limited the development of rainbow devices. Here, we observed the negative Goos-Hänchen effect in film samples across the entire visible spectrum. We also discovered an amber rainbow ribbon and an optical black hole due to perfect back reflection in optical waveguides, where little light leaks out. Not only does the amber rainbow ribbon effect show an automatic frequency selection response, as predicted by single frequency theoretical models and confirmed by experiments, it also shows spatial periodic regulation, resulting from broadband omnidirectional visible metamaterials prepared by disordered assembly systems. This broadband light trapping system could play a crucial role in the fields of optical storage and information processing when being used to construct ultra-compact modulators and other tunable devices.

Poincaré sphere trajectory encoding metasurfaces based on generalized Malus' law.

As a fundamental property of light, polarization serves as an excellent information encoding carrier, playing significant roles in many optical applications, including liquid crystal displays, polarization imaging, optical computation and encryption. However, conventional polarization information encoding schemes based on Malus' law usually consider 1D polarization projections on a linear basis, implying that their encoding flexibility is largely limited. Here, we propose a Poincaré sphere (PS) trajectory encoding approach with metasurfaces that leverages a generalized form of Malus' law governing universal 2D projections between arbitrary elliptical polarization pairs spanning the entire PS. Arbitrary polarization encodings are realized by engineering PS trajectories governed by either arbitrary analytic functions or aligned modulation grids of interest, leading to versatile polarization image transformation functionalities, including histogram stretching, thresholding and image encryption within non-orthogonal PS loci. Our work significantly expands the encoding dimensionality of polarization information, unveiling new opportunities for metasurfaces in polarization optics for both quantum and classical regimes.

Association of albumin to non-high-density lipoprotein cholesterol ratio with mortality in peritoneal dialysis patients.

OBJECTIVE: Malnutrition and inflammation are associated with mortality in peritoneal dialysis (PD) patients. Serum albumin and non-high-density lipoprotein cholesterol (non-HDL-C) are independently associated with mortality in PD patients. Combining albumin and non-HDL-C with mortality may be more plausible in clinical practice. METHODS: This retrospective cohort study included 1954 Chinese PD patients from 1 January 2009 to 31 December 2016. Kaplan-Meier curve was used to determine the relationship between albumin to non-HDL-C ratio and all-cause mortality. Cox regression analysis was applied to assess the independent predictive value while adjusting for confounding factors. Competitive risk analysis was used to examine the effects of other outcomes on all-cause mortality prognosis. RESULTS: In the 33-month follow-up period, there were 538 all-cause deaths. Kaplan-Meier analysis presented significant differences in all-cause mortality. Multivariate Cox regression showed that the risk of all-cause mortality was lower in the moderate group (9.36-12.79) (HR, 0.731; 95% CI, 0.593-0.902, p = 0.004) and the highest group (>12.79) (HR, 0.705; 95% CI, 0.565-0.879, p = 0.002) compared to the lowest group (≤9.36). Competitive risk analysis revealed significant differences for all-cause mortality (p < 0.001), while there was no statistical significance for other competing events. CONCLUSIONS: Low albumin to non-HDL-C ratio was associated with a high risk of all-cause mortality in PD patients. It may serve as a potential prognostic biomarker in PD patients.

Reversal of cholestatic liver disease by the inhibition of sphingosine 1-phosphate receptor 2 signaling.

Aims: The objective of this study is to examine the impact of inhibiting Sphingosine 1-phosphate receptor 2 (S1PR2) on liver inflammation, fibrogenesis, and changes of gut microbiome in the context of cholestasis-induced conditions. Methods: The cholestatic liver injury model was developed by common bile duct ligation (CBDL). Sprague-Dawley rats were randomly allocated to three groups, sham operation, CBDL group and JTE-013 treated CBDL group. Biochemical and histological assessments were conducted to investigate the influence of S1PR2 on the modulation of fibrogenic factors and inflammatory infiltration. We conducted an analysis of the fecal microbiome by using 16S rRNA sequencing. Serum bile acid composition was evaluated through the utilization of liquid chromatography-mass spectrometry techniques. Results: In the BDL rat model, the study findings revealed a significant increase in serum levels of conjugated bile acids, accompanied by an overexpression of S1PR2. Treatment with the specific inhibitor of S1PR2, known as JTE-013, resulted in a range of specific effects on the BDL rats. These effects included the improvement of liver function, reduction of liver inflammation, inhibition of hepatocyte apoptosis, and suppression of NETosis. These effects are likely mediated through the TCA/S1PR2/NOX2/NLRP3 pathway. Furthermore, the administration of JTE-013 resulted in an augmentation of the diversity of the bacterial community's diversity, facilitating the proliferation of advantageous species while concurrently inhibiting the prevalence of detrimental bacteria. Conclusions: The results of our study suggest that the administration of JTE-013 may have a beneficial effect in alleviating cholestatic liver disease and restoring the balance of intestinal flora.

Atherogenic index predicts all-cause and cardiovascular mortality in incident peritoneal dialysis patients.

BACKGROUND AND AIMS: Atherosclerosis, the main cause of cardiovascular disease (CVD), is prevalent in patients undergoing peritoneal dialysis (PD). Atherogenic index (AI) is a strong predictor of atherosclerosis. However, its prognostic value in CVD outcomes and all-cause mortality among patients undergoing PD remains uncertain. Therefore, we aimed to evaluate the association between AI and all-cause and CVD mortality in PD patients. METHODS: Calculated based on lipid profiles obtained through standard laboratory procedures, AI was evaluated in 2682 patients who underwent PD therapy between January 2006 and December 2017 and were followed up until December 2018. The study population was divided into four groups according to the quartile distribution of AI (Q1: <2.20, Q2: 2.20 to <2.97, Q3: 2.97 to <4.04, and Q4: ≥4.04). Multivariable Cox models were employed to explore the associations between AI and CVD and all-cause mortality was evaluated. RESULTS: During a median follow-up of 35.5 months (interquartile range, 20.9-57.2 months), 800 patients died, including 416 deaths from CVD. Restricted cubic splines showed non-linear relationship between AI and adverse clinical outcomes. The risks of all-cause and CVD mortality gradually increased across quartiles (log-rank, p < 0.001). After adjusting for potential confounders, the highest quartile (Q4) showed significantly elevated hazard ratio (HR) for both all-cause mortality (HR 1.54 [95% confidence interval (CI), 1.21-1.96]) and CVD mortality risk (HR 1.78 [95% CI, 1.26-2.52]), compared to the lowest quartile (Q1). CONCLUSIONS: AI was independently associated with all-cause and CVD mortality in patients undergoing PD, suggesting that AI might be a useful prognostic marker.

Association of Neutrophil and Albumin With Mortality Risk in Patients Receiving Peritoneal Dialysis.

OBJECTIVE: Inflammation and nutrition have been recognized as predicting mortality in patients receiving peritoneal dialysis (PD). Serum neutrophil and albumin are crucial factors in inflammation and nutrition status. Up until now, the synergistic effect of neutrophil and albumin on mortality prediction in PD patients is still being determined. Our study sought to assess the effect of the interaction between neutrophils and albumin on the risk of all-cause mortality and cardiovascular disease (CVD) mortality patients receiving PD. METHODS: A total of 1229 PD patients were recruited and divided into three categories in this cohort study. Their relationships with all-cause mortality and CVD mortality were analyzed in multivariable COX regression models adjusted for confounding factors. RESULTS: During the median follow-up of 34.2 months, 222 (18.1%) patients died, and 115 (51.8%) suffered from cardiovascular events. Patients with high neutrophil percentage-to-albumin ratio (NPAR) showed increased all-cause mortality and CVD mortality, with adjusted hazard ratios of 1.490 (95% confidence interval, 1.070-2.074, P = .018) and 1.633 (95% confidence interval, 1.041-2.561, P = .033), respectively, compared with those with low NPAR. Competitive risk models and sensitivity analyses further confirmed this association. In the receiver operating characteristic curve analysis, however, there was little evidence that NPAR is a better indicator than albumin and neutrophil count. CONCLUSIONS: Having a high NPAR is linked to a higher risk of mortality, especially when both high neutrophil and low albumin are present.

Extrahepatic Angiogenesis: A Potential Common Pathophysiological Basis of Multiple Organ Dysfunction in Rats with Cholestasis Cirrhosis.

BACKGROUND: In addition to intrahepatic angiogenesis, patients with cholestasis cirrhosis develop extrahepatic vasculature disorders and functional disturbances of multiple organ systems. Without effective intervention, these vascular disorders will eventually turn into multiple organs vascular syndromes, including the brain, lung and other organ systems. However, studies on the pathogenesis of vascular alterations among extrahepatic organ disturbances are still carried out separately, which hampered the successful translation of preclinical studies to the human setting and required further mechanistic insight into these complications. This study aims to investigate the relationship between extrahepatic angiogenesis and multiple organ impairment, and whether the vascular endothelial growth factor (VEGF) family members and their receptors are involved in this process. METHODS: Pathological changes of the multiple organs were determined by histopathological and immunohistochemical staining in the established common bile duct ligation (CBDL) rats, and angiogenesis was estimated by microvessel density (MVD). Levels of the VEGF family members and their receptors in the serum and organ tissues were also measured by using enzyme-linked immunosorbent assays. RESULTS: The MVD and VEGF family members and their receptors were significantly increased in CBDL rats with multiple organ injury, especially in the liver, lung and cerebral cortex. Meanwhile, we noticed moderate elevation of soluble receptor of the vascular endothelial growth factor-1 (sFlt-1) in the liver, lung, and cerebral cortex, whereas the levels of placental growth factor (PLGF) increased significantly. CONCLUSIONS: Extrahepatic angiogenesis may represent a common pathophysiological basis for multiple organ dysfunction and the sFlt-1/PLGF ratio could offer an avenue for further studies to target extrahepatic angiogenesis in cholestatic cirrhosis.

A novel 22-bp InDel within FGF7 gene is significantly associated with growth traits in goat.

Fibroblast growth factor 7 (FGF7) is involved in lipid metabolism, which is considered as a candidate gene with close relation with muscle development by eGWAs and RNA-Seq analyses. To date, limited research has been conducted on the relationship between FGF7 gene and growth traits. The main objective of this work was to further investigate the association between novel InDel within FGF7 gene and growth traits in goat. Herein, FGF7 mRNA expression levels were investigated in various Fuqing goat tissues. We found that FGF7 gene was expressed in six adult goat tissues with the highest mRNA levels in adipose tissue. This result suggested that FGF7 gene might play a critical role in fat deposition. We also detected potential polymorphisms in Fuqing, Nubian and Jianyang Daer breeds. A 22-bp InDel polymorphism in FGF7 gene was detected in 396 goats and the three genotypes were designated as II, ID, and DD. Correlation analysis revealed that InDel polymorphism was significantly associated with growth traits (P < 0.05). Goats with genotypes ID and/or II had superior growth traits compared to those with genotype DD. In summary, our findings suggested that the 22-bp InDel within FGF7 gene could act as a molecular marker to improve the growth traits of goats in breeding programs.

Serum uric acid to creatinine ratio as a risk factor for mortality among patients on continuous ambulatory peritoneal dialysis: a multi-center retrospective study.

BACKGROUND: Serum uric acid to serum creatinine ratio (SUA/Scr) has emerged as a new biomarker, which is significantly associated with several metabolic diseases. However, no study has investigated the association between SUA/Scr and mortality among patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: In this multicenter retrospective cohort study, we enrolled CAPD patients in eight tertiary hospitals in China from 1 January 2005 to 31 May 2021. Cox proportional hazard models were used to determine the relationship between SUA/Scr and mortality. RESULTS: A total of 2480 patients were included; the mean age was 48.9 ± 13.9 years and 56.2% were males. During 12648.0 person-years of follow-up, 527 (21.3%) patients died, of which 267 (50.7%) deaths were caused by cardiovascular disease. After multivariable adjustment for covariates, per unit increase in SUA/Scr was associated with a 62.9% (HR, 1.629 (95% confidence interval (CI) 1.420-1.867)) and 73.0% (HR, 1.730 (95% CI 1.467-2.041)) higher risk of all-cause and cardiovascular mortality. Results were similar when categorized individuals by SUA/Scr quartiles. Compared with the lowest quartile of SUA/Scr, the highest and the second highest quartile of SUA/Scr had a 2.361-fold (95% CI 1.810-3.080) and 1.325-fold (95% CI 1.003-1.749) higher risk of all-cause mortality, as well as a 3.701-fold (95% CI 2.496-5.489) and 2.074-fold (95% CI 1.387-3.100) higher risk of cardiovascular mortality. Multivariable-adjusted spline regression models showed nonlinear association of SUA/Scr with mortality in CAPD patients. CONCLUSIONS: Higher levels of SUA/Scr were associated with higher risk of all-cause and cardiovascular mortality in CAPD patients.

Detection distribution of CNVs of SNX29 in three goat breeds and their associations with growth traits.

As a member of the SNX family, the goat sorting nexin 29 (SNX29) is initially identified as a myogenesis gene. Therefore, this study aimed to examine the polymorphism in the SNX29 gene and its association with growth traits. In this study, we used an online platform to predict the structures of the SNX29 protein and used quantitative real-time PCR to detect potential copy number variation (CNV) in Shaanbei white cashmere (SBWC) goats (n = 541), Guizhou black (GB) goats (n = 48), and Nubian (NB) goats (n = 39). The results showed that goat SNX29 protein belonged to non-secretory protein. Then, five CNVs were detected, and their association with growth traits was analyzed. In SBWC goats, CNV1, CNV3, CNV4, and CNV5 were associated with chest width and body length (P < 0.05). Among them, the CNV1 individuals with gain and loss genotypes were superior to those individuals with a median genotype, but CNV4 and CNV5 of individuals with the median genotype were superior to those with the loss and gain genotypes. In addition, individuals with the gain genotype had superior growth traits in CNV3. In brief, this study suggests that the CNV of SNX29 can be used as a molecular marker in goat breeding.

A new, feasible, and convenient method based on semantic segmentation and deep learning for hemoglobin monitoring.

Objective: Non-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input. Methods: Surgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R2, explained variance score (EVS), and mean absolute error (MAE). Results: A total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R2, EVS, and MAE of 0.503 (95% CI, 0.499-0.507), 0.518 (95% CI, 0.515-0.522) and 1.6 g/dL (95% CI, 1.6-1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R2: 0.509, EVS:0.516, MAE:1.6 g/dL). Conclusion: We developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on.

Serum Soluble Vascular Endothelial Growth Factor Receptor 1 as a Potential Biomarker of Hepatopulmonary Syndrome.

Background and Aims: The results of basic research implicate the vascular endothelial growth factor (VEGF) family as a potential target of hepatopulmonary syndrome (HPS). However, the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS. Therefore, we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies. Methods: Clinically, patients with chronic liver disease from two medical centers were enrolled and examined for HPS. Patients were divided into HPS, intrapulmonary vascular dilation [positive contrast-enhanced echocardiography (CEE) and normal oxygenation] and CEE-negative groups. Baseline information and perioperative clinical data were compared between HPS and non-HPS patients. Serum levels of VEGF family members and their receptors were measured. In parallel, HPS rats were established by common bile duct ligation. Liver, lung and serum samples were collected for the evaluation of pathophysiologic changes, as well as the expression levels of the above factors. Results: In HPS rats, all VEGF family members and their receptors underwent significant changes; however, only soluble VEGFR1 (sFlt-1) and the sFlt-1/ placental growth factor (PLGF) ratio were changed in almost the same manner as those in HPS patients. Furthermore, through feature selection and internal and external validation, sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients. Conclusions: Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.

Combined influence of depression and low-grade inflammation on mortality in peritoneal dialysis patients.

BACKGROUND: The relationship between depression and systemic inflammation as risk factors for mortality is not well understood and requires further investigation. METHODS: Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) between July 01, 2015 to December 31, 2019, were analyzed and followed up until December 31, 2020. According to their status of depression (PHQ-9 score ≥ 5) and low-grade inflammation (hs-CRP level ≥ 3 mg/L), patients were divided into four groups (G1, without depression, nor inflammation; G2, with depression, without inflammation; G3, with inflammation, without depression; G4, with both depression and inflammation). We performed Kaplan-Meier and multivariable Cox proportional analyses of mortality for the combined influence of depression and systemic inflammation in this cohort. RESULTS: During the mean follow-up of 36.3 ± 14.8 months, 73 deaths were recorded in 358 participants. Compared with patients in group G1, patients in group G2 and G3 carried 137% {hazard ratio (HR): 2.37, 95% confidence interval (CI): 1.06-5.23, p = 0.035} and 140% (HR: 2.40, 95% CI: 1.01-5.69, p = 0.048) higher risk of mortality. Patients in group G4 (with both depression and inflammation) showed the highest risks of all-cause mortality with 276% higher mortality risk (HR: 3.76, 95% CI: 1.73-8.15, p = 0.001), respectively. CONCLUSION: The combined of depression and inflammation is associated with all-cause mortality in peritoneal dialysis patients, suggesting a need for further study of depression and low-grade inflammation in PD patients and potential relationship between them.

Clinical significance of serum glucose to lymphocyte ratio as a prognostic marker in peritoneal dialysis patients.

BACKGROUND: The glucose-to-lymphocyte ratio (GLR), a glucose metabolism and systemic inflammatory response parameter, is associated with an adverse prognosis for various diseases. However, the association between serum GLR and prognosis in patients undergoing peritoneal dialysis (PD) is poorly understood. METHODS: In this multi-center cohort study, 3236 PD patients were consecutively enrolled between 1 January 2009 and 31 December 2018. Patients were divided into four groups according to the quartiles of baseline GLR levels (Q1: GLR ≤ 2.91, Q2:2.91 < GLR ≤ 3.91, Q3:3.91 < GLR < 5.59 and Q4: GLR ≥ 5.59). The primary endpoint was all-cause and cardiovascular disease (CVD) related mortality. The correlation between GLR and mortality was examined using Kaplan-Meier and multivariable Cox proportional analyses. RESULTS: During the follow-up period of 45.93 ± 29.01 months, 25.53% (826/3236) patients died, of whom 31% (254/826) were in Q4 (GLR ≥ 5.59). Multivariable analysis revealed that GLR was significantly associated with all-cause mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p = .019) and CVD mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p = .04). Compared with the Q1 (GLR ≤ 2.91), placement in Q4 was associated with an increased risk of all-cause mortality (adjusted HR: 1.26, 95% CI: 1.02 ∼ 1.56, p = .03) and CVD mortality (adjusted HR 1.76; CI 1.31 ∼ 2.38, p < .001). A nonlinear relationship was found between GLR and all-cause or CVD mortality in patients undergoing PD (p = .032). CONCLUSION: A higher serum GLR level is an independent prognostic factor for all-cause and CVD mortality in patients undergoing PD, suggesting that more attention should be paid to GLR.

Multifunctional Metasurfaces Enabled by Multifold Geometric Phase Interference.

Geometric phase is frequently used in artificially designed metasurfaces; it is typically used only once in reported works, leading to conjugate responses of two spins. Supercells containing multiple nanoantennas can break this limitation by introducing more degrees of freedom to generate new modulation capabilities. Here, we provide a method for constructing supercells for geometric phases using triple rotations, each of which achieves a specific modulation function. The physical meaning of each rotation is revealed by stepwise superposition. Based on this idea, spin-selective holography, nanoprinting, and their hybrid displays are demonstrated. As a typical application, we have designed a metalens that enables spin-selective transmission, allowing for high-quality imaging with only one spin state, which can serve as a plug-and-play chiral detection device. Finally, we analyzed how the size of supercells and the phase distribution inside it can affect the higher order diffraction, which may help in designing supercells for different scenarios.

Total cholesterol and mortality in peritoneal dialysis: a retrospective cohort study.

BACKGROUND: Total cholesterol is inversely associated with mortality in dialysis patients, which seems implausible in real-world clinical practice. May there be an optimal range of total cholesterol associated with a lower mortality risk? We aimed to evaluate the optimal range for peritoneal dialysis (PD) patients. METHODS: We conducted a retrospective real-world cohort study of 3565 incident PD patients from five PD centers between January 1, 2005, and May 31, 2020. Baseline variables were collected within one week before the start of PD. The associations between total cholesterol and mortality were examined using cause-specific hazard models. RESULTS: 820 (23.0%) patients died, including 415 cardiovascular deaths, during the follow-up period. Restricted spline plots showed a U-curved association of total cholesterol with mortality. Compared with the reference range (4.10-4.50 mmol/L), high levels of total cholesterol (> 4.50 mmol/L) were associated with increased risks of all-cause (hazard ratio [HR] 1.35, 95% confidence index [CI] 1.08-1.67) and cardiovascular mortality (HR 1.38, 95% CI 1.09-1.87). Similarly, compared with the reference range, low levels of total cholesterol (< 4.10mmol/L) were also associated with high risks of all-cause (HR 1.62, 95% CI 1.31-1.95) and cardiovascular mortality (HR 1.72, 95% CI 1.27-2.34). CONCLUSION: Total cholesterol levels at the start of PD between 4.10 and 4.50 mmol/L (158.5 to 174.0 mg/dL), an optimal range, were associated with lower risks of death than higher or lower levels, resulting in a U-shaped association.

Remnant cholesterol as a risk factor for all-cause and cardiovascular mortality in incident peritoneal dialysis patients.

BACKGROUND AND AIMS: Remnant cholesterol (RC) adversely contributes to cardiovascular disease (CVD) and overall survival in various diseases. However, its role in CVD outcomes and all-cause mortality in patients undergoing peritoneal dialysis (PD) is limited. Therefore, we aimed to investigate the association between RC and all-cause and CVD mortality in patients undergoing PD. METHODS AND RESULTS: Based on lipid profiles recorded using standard laboratory procedures, fasting RC levels were calculated in 2710 incident patients undergoing PD who were enrolled between January 2006 and December 2017 and followed up until December 2018. Patients were divided into four groups according to the quartile distribution of baseline RC levels (Q1: <0.40 mmol/L, Q2: 0.40 to <0.64 mmol/L, Q3: 0.64 to <1.03 mmol/L, and Q4: ≥1.03 mmol/L). Associations between RC and CVD and all-cause mortality were evaluated using multivariable Cox models. During the median follow-up period of 35.4 months (interquartile range, 20.9-57.2 months), 820 deaths were recorded, of which 438 were CVD-related. Smoothing plots showed non-linear relationships between RC and adverse outcomes. The risks of all-cause and CVD mortality increased progressively through the quartiles (log-rank, p < 0.001). Using adjusted proportional hazard models, a comparison of the highest (Q4) to lowest (Q1) quartiles revealed significant increases in the hazard ratio (HR) for all-cause mortality (HR 1.95 [95% confidence interval (CI), 1.51-2.51]) and CVD mortality risk (HR 2.60 [95% CI, 1.80-3.75]). CONCLUSION: An increased RC level was independently associated with all-cause and CVD mortality in patients undergoing PD, suggesting that RC was important clinically and required further research.

Pan-immune-inflammation value is associated with poor prognosis in patients undergoing peritoneal dialysis.

BACKGROUND: Immune-inflammatory biomarkers (IIBs) have been shown to be correlated with prognosis in patients undergoing peritoneal dialysis (PD). In this study, we aimed to evaluate the relationship between a novel comprehensive biomarker, the pan-immune-inflammation value (PIV), and the prognosis of patients undergoing PD. METHODS: We retrospectively analyzed data from a multicenter, large-sample PD database. PIV was calculated as (neutrophil count × platelet count × monocyte count)/lymphocyte count. The prognostic endpoints in this study were all-cause death all-cause, cardiovascular disease (CVD) and infection-related death. The Kaplan-Meier method, a Cox proportional hazards regression, Fine-Gray competing risk model, smooth curve, and subgroup analysis were used to analyze the independent relationship between PIV and the prognosis of patients undergoing PD. RESULTS: A total of 2796 cases of PD were included, and the study population was divided into Tertiles 1, 2, and 3, according to the tertiles of baseline PIVs. After adjusting for multiple model factors, patients in the Tertile 3 group had a significantly higher risk of all-cause death, CVD death and infection-related death compared with patients with PIV in the Tertile 1 group. Interaction tests showed no positive correlations for subgroup parameters. Regarding all-cause death, compared with the lowest tertile, the multivariable-adjusted hazard ratios (95% confidence intervals) of the highest and middle tertiles were 1.55 (1.25-1.94) and 1.77 (1.43-2.19), respectively; PIV (log2 processing) was associated with 17% excess of mortality in the continuous model. CONCLUSIONS: A high PIV at baseline was significantly associated with an increased risk of deaths due to all-causes, CVD and infection in patients undergoing PD.