Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Metabolomics revealed more deleterious toxicity induced by the combined exposure of ammonia and nitrite on Ruditapes philippinarum compared to single exposure.

NH3-N and NO2-N always co-exist in the aquatic environment, but there is not a clear opinion on their joint toxicities to the molluscs. Presently, clams Ruditapes philippinarum were challenged by environmental concentrations of NH3-N and NO2-N, singly or in combination, and analyzed by metabolomics approaches, enzyme assays and transmission electron microscope (TEM) observation. Results showed that some same KEGG pathways with different enriched-metabolites were detected in the three exposed groups within one day, and completely different profiles of metabolites were found in the rest of the exposure period. The combined exposure induced heavier and more lasting toxicities to the clams compared with their single exposure. ACP activity and the number of secondary lysosomes were significantly increased after the combined exposure. The present study shed light on the joint-toxicity mechanism of NH3-N and NO2-N, and provided fundamental data for the toxicity research on inorganic nitrogen.

Xinyang tablet ameliorates sepsis-induced myocardial dysfunction by regulating Beclin-1 to mediate macrophage autophagy and M2 polarization through LncSICRNT1 targeting E3 ubiquitin ligase TRAF6.

OBJECTIVE: Xinyang Tablet (XYT) has emerged as a potential intervention to counter sepsis-induced myocardial dysfunction (SMID) by influencing macrophage autophagy and M2 polarization. This study aimed to unravel the underlying mechanism of XYT in sepsis-induced myocardial dysfunction (SIMD). METHODS: A microarray analysis was employed to explore sepsis-related changes, and bioinformatics analysis was used to predict lncRNAs binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). This studio utilized SIMD mouse models induced by lipopolysaccharide (LPS) injection, followed by treatments involving varied doses of XYT, digoxin (positive control), or si-LncSICRNT1. After seven days, evaluations encompassing mouse hair/mental state/diet/weight were measured, and cardiac function via echocardiography were conducted. Myocardial tissue changes were observed using hematoxylin-eosin staining. Additionally, bone marrow-derived macrophages (BMDMs) subjected to LPS for M1 polarization were treated with oe-LncSICRNT1, si-TRAF6 and their negative control, XYT, or autophagy inhibitor 3-Methyladenine (3-MA) (positive control). RT-qPCR and Western blot analyses were employed to assess LncSICRNT1, TRAF6, Beclin-1, LC3II/LC3I, and p62 levels. Immunohistochemistry and flow cytometry were used for M1/M2 polarization markers, while enzyme-linked immunosorbent assay (ELISA) gauged inflammatory factor levels. Interaction between TRAF6 and LncSICRNT1 was probed using RNA pull-down and RNA immunoprecipitation (RIP) assays. RESULTS: Chip analysis obtained 1463 differentially expressed lncRNAs, including LINC01550 (LncSICRNT1). Further prediction indicated that LncSICRNT1 was highly likely to directly bind to TRAF6. XYT treatment in LPS-induced SIMD mice led to notable enhancements in sleep/hair/diet/activity, increased weight/left ventricular end-diastolic diameter (LVEDd)/LV ejection fraction (LVEF)/LV fraction shortening (LVFS). These improvements were associated with elevated LncSICRNT1 expression and decreased TRAF6 protein levels, culminating in reduced myocardial inflammatory responses and improved cardiac function. Notably, XYT was found to suppress macrophage M1 polarization, while enhancing M2 polarization, ultimately benefitting cardiac function via LncSICRNT1 modulation. Furthermore, the study revealed LncSICRNT1 modulated Beclin-1 ubiquitination and restrained macrophage autophagy by targeting TRAF6 expression. CONCLUSION: The study highlights XYT's potential to ameliorate LPS-induced SIMD by elevating LncSICRNT1 expression, influencing TRAF6 expression, and regulating Beclin-1 ubiquitination. These actions collectively inhibit macrophage autophagy and foster M1/M2 polarization, contributing to cardiac function improvement.

The correlation of urinary strontium with the risk of chronic kidney disease among the general United States population.

Background: This study sought to illustrate whether urinary strontium levels were related to developing chronic kidney disease (CKD) in the United States population. Methods: A total of 5,005 subjects were identified from the National Health and Nutrition Examination Survey 2011-2016. Survey-weighted logistic regression analysis, multivariate linear regression analysis, restricted cubic spline (RCS) plots curve and stratified analyses were undertaken to explicate the correlation between urinary strontium and CKD. Results: With the increase of urinary strontium, the incidence rate of CKD and urinary albumin to creatinine ratio (UACR) levels gradually decreased, and estimated glomerular filtration rate (eGFR) levels gradually increased. After controlling all confounders, only urinary strontium in the fourth quartile was correlated to a lower CKD prevalence (OR: 0.59; 95% CI, 0.44-0.79) compared to the lowest quartile. Multivariate linear regression analysis showed that urinary strontium was positively correlated with eGFR but negatively with UACR. RCS curve suggested a nonlinear relationship between urinary strontium and CKD (P for non-linearity <0.001). Stratified analyses indicated no significant difference in the correlation between urinary strontium and CKD among different subgroups. Conclusion: Urinary strontium was strongly correlated with a low risk of CKD, and this association was non-linear among the US population.

Comparative analysis of microRNA expression profiles in clam Ruditapes philippinarum after ammonia nitrogen exposure.

Ammonia nitrogen is a long-lasting pollutant along the Chinese coast. In our previous studies, the clam Ruditapes philippinarum exhibited several toxic responses to environmental concentrations of ammonia nitrogen. To elucidate the underlying mechanism of ammonia nitrogen toxicity in clams at the post-transcriptional level, microRNA (miRNA) expression profiles were investigated by high-throughput sequencing after the clams were exposed to 0.1 mg/L ammonia nitrogen for 30 days. A total of 238 miRNAs were identified, including 49 conserved miRNAs and 189 novel miRNAs. After comparative analysis, six miRNAs were significantly expressed after 1 day of exposure, with three up-regulated and three down-regulated miRNAs. In addition, 35 miRNAs were significantly expressed after 30 days of exposure, of which 16 were up-regulated and 19 were down-regulated. Furthermore, the target genes of each differentially expressed miRNA were predicted, followed by Gene Ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The target genes were predicted to be involved in the immune response, protein processing and transport, DNA damage repair, cellular communication, neural signaling, redox homeostasis, lipid metabolism, and biotransformation. A biological phagocytosis assay proved the speculation that ammonia nitrogen regulated the immunity of clams with the aid of a novel miRNA (novel_29). These findings support further research on miRNA levels in R. philippinarum exposed to ammonia nitrogen.

Role of adrenal venous sampling in the differential diagnosis and treatment protocol of ACTH-independent Cushing's syndrome with bilateral adrenal lesions.

PURPOSE: The diagnosis and management of adrenocorticotropic hormone-independent Cushing's syndrome (AICS) with bilateral adrenal lesions remain challenging. Some studies have explored the value of adrenal vein sampling (AVS) in patients with AICS; however, more investigations are needed to assess its benefits for diagnosis and treatment planning in this population. METHODS: Thirteen patients with clinical, biochemical and imaging evidence of AICS with bilateral adrenal lesions underwent AVS in our department from 2017-2022 were recruited. Only the data from nine patients for whom AVS succeeded were finally included in this study and further analyzed. Blood samples were successfully collected from both adrenal veins (AV) and inferior vena cava (IVC) in these nine patients, and the levels of plasma total cortisol (PTC) and plasma aldosterone concentrations (PAC) were measured. The ratio of the PAC of the AV to the IVC was calculated, and the PTC to PAC ratios were compared between AV. The surgical strategy was chosen according to the results of AVS. Postoperative histology and immunohistochemistry of the adrenal tissues were performed. The prognosis was evaluated based on the improvement of clinical symptoms and biochemical parameters (including PTC and ACTH measurements). RESULTS: Patients with AICS were clinically diagnosed based on clinical signs, results of functional tests and the presence of bilateral adrenal lesions as observed on computed tomography imaging. An AV to IVC PAC ratio greater than 2 confirmed successful AVS. The PTC to PAC ratio (high side to low side) was greater than 2 in four patients, and less than 2 in five patients. The postoperative pathological results were consistent with clinical diagnosis and AVS. During the mean follow-up of 33 months, all nine patients achieved varying degrees of clinical improvement. CONCLUSION: Our study showed that AVS helped to distinguish unilateral and bilateral lesions, identify the laterality of the autonomous hypercortisolism, and improve therapeutic strategy selection in patients with AICS and bilateral adrenal lesions.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study.

OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS: ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

The Mechanism of SNHG8/Microrna-421-3p/Sorting Nexin 8 Axis on Dopaminergic Neurons in Substantia Nigra in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the aging population. Particularly, long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in PD, while the role of lncRNA SNHG8 in PD remains to be further explored. C57BL/6 mice were induced by rotenone to establish a PD model in vivo, and then the dopaminergic (DA) neuronal damage and locomotor dysfunction in rotenone-treated mice were evaluated. Murine DA cell line MN9D was treated with rotenone to establish a cellular PD model in vitro. Then, the viability, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells were assessed. Expression levels of SNHG8, microRNA-421-3p (miR-421-3p), and sorting nexin 8 (SNX8) in the substantia nigra (SN) of PD mice and rotenone-treated MN9D cells were detected. The interaction between SNHG8 and miR-421-3p, and the targeting relationship between SNX8 and miR-421-3p were confirmed. SNHG8 and SNX8 expression levels were decreased while miR-421-3p expression level was increased in the SN of PD mice and rotenone-treated MN9D cells. Upregulated SNHG8 ameliorated dopaminergic neuron damage and locomotor dysfunction in PD mice. Meanwhile, upregulated SNHG8 enhanced viability, diminished apoptosis, and alleviated mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy in rotenone-treated MN9D cells. Mechanistically, SNHG8 bound to miR-421-3p, and miR-421-3p targeted SNX8. Overexpressed SNHG8 downregulates miR-421-3p to alleviate rotenone-induced dopaminergic neuron injury in PD via upregulating SNX8.

A protein inhibitor of activated STAT (CgPIAS) negatively regulates the expression of ISGs by inhibiting STAT activation in oyster Crassostrea gigas.

The protein inhibitor of activated STAT (PIAS) family proteins act as the important negative regulators in janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which can be also involved in regulating the expression of interferon-stimulated genes (ISGs). In the present study, a PIAS homologue (designated as CgPIAS) was identified from oyster Crassostrea gigas. The open reading frame (ORF) of CgPIAS cDNA was of 1887 bp encoding a peptide of 628 amino acid residues. The CgPIAS protein contains a conserved scaffold attachment factor A/B/acinus/PIAS (SAP) domain, a Pro-Ile-Asn-Ile-Thr (PINIT) motif, a RING-finger-like zinc-binding domain (RLD) and two SUMO-interaction Motifs (SIMs). The deduced amino acid sequence of CgPIAS shared 74.58-81.36% similarity with other PIAS family members in the RLD domain. The mRNA transcripts of CgPIAS were detected in all the tested tissues with highest level in haemocytes (32.98-fold of mantles, p < 0.001). After poly (I:C) and recombinant Interferon-like protein (rCgIFNLP) stimulation, the mRNA expression of CgPIAS in haemocytes significantly up-regulated to the highest level at 48 h (7.38-fold, p < 0.001) and at 24 h (13.08-fold, p < 0.01), respectively. Moreover, the nuclear translocation of CgPIAS was observed in haemocytes after poly (I:C) stimulation. Biolayer Interferometry (BLI) assay revealed that the recombinant protein CgPIAS-RLD could interact with the recombinant protein CgSTAT in vitro with the KD value of 3.88 × 10-8 M. In the CgPIAS-RNAi oysters, the green signals of CgSTAT protein in nucleus of haemocytes increased compared with that in NC-RNAi group, and the mRNA expression of myxovirus resistance (CgMx1), oligoadenylate synthase-like proteins (CgOASL), CgViperin and IFN-induced protein 44-like (CgIFI44L-1) in haemocytes significantly increased at 12 h after poly (I:C) stimulation, which were 2.39-fold (p < 0.05), 2.18-fold (p < 0.001), 1.74-fold (p < 0.05), and 2.89-fold (p < 0.01) of that in control group, respectively. The above results indicated that CgPIAS negatively regulated the ISG expression by inhibiting STAT activation in oyster C. gigas.

Comprehensive overview of Nrf2-related epigenetic regulations involved in ischemia-reperfusion injury.

Ischemic disease is a class of diseases in which an organ is ischemic due to vascular occlusion, a major contributor to death and disability worldwide. However, when the blood flow is restored, more severe damage occurs than ischemia alone and is known as ischemic-reperfusion injury (IRI). During reperfusion, the imbalance between the production of reactive oxygen species (ROS) and buffering capacity of the antioxidant defense system results in cell damage and death. Nuclear factor E2-related factor 2 (Nrf2) significantly affects antioxidant stress damage. The function of Nrf2 in the pathological process of IRI has been widely discussed, but the impact of epigenetic modifications associated with Nrf2 remains unclear. This article provides a comprehensive overview of the role and mechanism of Nrf2-related epigenetic modifications in the IRI of various organs, including the brain, heart, liver, and kidney. In addition, we summarize agonists that may target epigenetic regulation of Nrf2, which may be beneficial in seeking more effective strategies to improve IRI.

Clinical Significance of HSCARG for Atherosclerotic Coronary Heart Disease and Reduced ROS-Oxidative Stress in in Vivo and in Vitro Models via p47phox by NF-κB Activity

ABSTRACT Introduction: Coronary heart disease (CHD) is a dynamic process in which there are interactions between endothelial dysfunction, oxidative stress, and inflammatory responses. The aim of the present study was to investigate the function and mechanism of HSCARG in the treatment of CHD. Methods: Male apolipoprotein E/low-density lipoprotein receptor-deficient mice were given a high-fat diet with 21% fat and 0.15% cholesterol for the in vivo model. Human umbilical vein endothelial cells were incubated with angiotensin II for the in vitro model. HSCARG expression was inhibited in patients or mice with CHD. Results: HSCARG reduced oxidative stress in mice with CHD. HSCARG also reduced reactive oxygen species (ROS)-oxidative stress in the in vitro model. HSCARG induced p47phox expression in the in vitro model by NF-κB activity. The regulation of nuclear factor kappa B (NF-κB) activity or p47phox expression participates in the effects of HSCARG in CHD. Conclusion: Altogether, our data indicate that HSCARG reduced ROS-oxidative stress in in vivo and in vitro models of CHD via p47phox by NF-κB activity and may be a clinical target for CHD.

Clinical Significance of HSCARG for Atherosclerotic Coronary Heart Disease and Reduced ROS-Oxidative Stress in in Vivo and in Vitro Models via p47phox by NF-κB Activity.

INTRODUCTION: Coronary heart disease (CHD) is a dynamic process in which there are interactions between endothelial dysfunction, oxidative stress, and inflammatory responses. The aim of the present study was to investigate the function and mechanism of HSCARG in the treatment of CHD. METHODS: Male apolipoprotein E/low-density lipoprotein receptor-deficient mice were given a high-fat diet with 21% fat and 0.15% cholesterol for the in vivo model. Human umbilical vein endothelial cells were incubated with angiotensin II for the in vitro model. HSCARG expression was inhibited in patients or mice with CHD. RESULTS: HSCARG reduced oxidative stress in mice with CHD. HSCARG also reduced reactive oxygen species (ROS)-oxidative stress in the in vitro model. HSCARG induced p47phox expression in the in vitro model by NF-κB activity. The regulation of nuclear factor kappa B (NF-κB) activity or p47phox expression participates in the effects of HSCARG in CHD. CONCLUSION: Altogether, our data indicate that HSCARG reduced ROS-oxidative stress in in vivo and in vitro models of CHD via p47phox by NF-κB activity and may be a clinical target for CHD.

Modifications of calcium metabolism and apoptosis after ammonia nitrogen exposure imply a tumorous fate in clam Ruditapes philippinarum?

Ammonia nitrogen (NH3N) is a kind of toxic inorganic nitrogen that has been a great ecological stressor to the marine organisms for quite a few years in Chinese coastal area. Toxic mechanism of ammonia nitrogen on marine bivalve is not well elucidated, especially in calcium metabolism and apoptosis. In the present study, clams Ruditapes philippinarum were used as the experiment animals to receive NH3N exposure with environmental concentrations for 21 days. Results showed that NH3N exposure induced ROS production, decreased Ca2+ concentration, and increased caspase 3 activities in the clam gill cells. In addition, three kinds of Ca2+ exchanger genes, e. g. Na+/K+/Ca2+ exchanger 2, Na+/Ca2+ exchanger 3 and monovalent cation/H+ antiporter, exhibited significant increments in transcription to eliminate intracellular Ca2+. Besides, NH3N exposure significantly increased mRNA expression levels of key anti-apoptotic regulator Bcl-2 genes (Bcl2-1 and Bcl2-1), which would inhibit the apoptosis degree in gill cells. Taken together, increased Ca2+-extrusion and apoptosis inhibition would act cooperatively to alleviate the apoptosis degree and extend the lifespan, so that some kind of tumor might develop in oxidative damaged gill cells after NH3N exposure. Therefore, it is predicted that NH3N exposure will probably bring the clam R. philippinarum a tumorous fate, which will be a great challenge for the healthy development of molluscs aquaculture under the current pollution condition. In addition, caspase 3 activity and mRNA expression levels of Bcl2-2 and Na+/Ca2+ exchanger 3 could be used as potential clam biomarkers to indicate NH3N pollution.

Status and factors related to post-traumatic growth in continuous ambulatory peritoneal dialysis: A multi-centre study.

AIM: To investigate the extent of post-traumatic growth, and the correlation between post-traumatic growth and self-perceived stress, post-traumatic growth and self-perceived burden among CAPD patients. DESIGN: A cross-sectional study. METHODS: This was a multi-centre study including 752 patients from 44 hospitals. Self-perceived stress, self-perceived burden and post-traumatic growth were measured using the post-traumatic growth inventory (PTGI), the Chinese version of the perceived stress questionnaire (CPSQ) and the self-perceived burden scale (SPBS). A multiple stepwise regression analysis was fit with the total PTGI score as the outcome of interest. RESULTS: Patients concurrently experienced post-traumatic growth and stress following peritoneal dialysis. The initiation of patients' education level, employment status and self-perceived stress were all found to relate to growth among Chinese CAPD patients. There was not sufficient evidence to suggest that self-perceived burden was related to experiencing growth.

A myxovirus resistance like protein involved in CgIFNLP mediated immune response of oyster Crassostrea gigas.

The myxovirus resistance (Mx) proteins belong to interferon (IFN)-induced dynamin GTPase and play a pivotal role in the inhibition of replication of numerous viruses. In the present study, an Mx homologue (designated as CgMx1) was identified from oyster Crassostrea gigas. The open reading frame (ORF) of CgMx1 cDNA was of 1689 bp encoding a peptide of 562 amino acid residues. There was an N-terminal dynamin GTPase domain in the predicted peptide, which consisted of a tripartite GTP-binding motif (GDXXSGKS, DLPG and T/NKXD). The deduced amino acid sequence of CgMx1 shared 30-39% similarity with other Mx family members. And CgMx1 was clustered with Mx from H. discus, and then assigned into the invertebrate branch of the phylogenetic tree. The mRNA transcripts of CgMx1 were constitutively distributed in all the tested tissues, with the highest level in haemocytes (1342.45-fold of labial palps, p < 0.05). The mRNA expression of CgMx1 in haemocytes was significantly up-regulated to the highest level at 6 h (13.14-fold, p < 0.001) after poly (I:C) treatment and at 24 h (66.28-fold, p < 0.001) after recombinant IFN-like protein (rCgIFNLP) stimulation, respectively. CgMx1 protein was found to distribute in both the cytoplasm and nucleus of haemocytes. In the oysters with CgIFNLP and signal transducer and activator of transcription (CgSTAT) silenced by RNAi, the mRNA expression of CgMx1 decreased significantly in the haemocytes at 12 h after poly (I:C) stimulation, which was 0.02-fold and 0.04-fold of that in EGFP-RNAi oysters (p < 0.001), respectively. Meanwhile, EMSA assay revealed that CgSTAT was able to transactivate CgMx1 promoter through directly binding to its interferon-stimulated response element (ISRE) and gamma interferon activation site (GAS). The above results indicated that CgMx1 participated in the immune response of C. gigas through the signal pathway mediated by CgIFNLP and CgSTAT.

The Value of Different Single or Combined Indexes of the Captopril Challenge Test in the Diagnosis of Primary Aldosteronism.

Objective: The result interpretation of the captopril challenge test (CCT) for the diagnosis of primary aldosteronism (PA) is not standardized. Superiorities of different indexes in the CCT have not been fully investigated. We aimed to comprehensively evaluate the value and influence factors of different CCT-associated indexes in the diagnosis of PA. Methods: We enrolled 312, 85, 179 and 97 patients in the groups of PA, essential hypertension (EH), unilateral PA (UPA) and bilateral PA (BPA), respectively. For each single index investigated, we computed diagnostic estimates including the area under the receiver operating characteristic curve (AUC). We performed pre-specified subgroup analyses to explore influence factors. We assessed the diagnostic value of combined indexes in binary logistic regression models. Results: Post-CCT aldosterone to renin ratio (ARR) (AUC = 0.8771) and plasma aldosterone concentration (PAC) (AUC = 0.8769) showed high value in distinguishing PA from EH, and their combination (AUC = 0.937) was even superior to either alone. The diagnostic efficacy was moderately high for post-CCT aldosterone to angiotensin II ratio (AA2R) (AUC = 0.834) or plasma renin activity (PRA) (AUC = 0.795) but low for the suppression percentage of PAC (AUC = 0.679). Post-CCT PAC had a significantly higher AUC in the UPA than BPA subgroup (AUC = 0.914 vs 0.827, P<0.05). Conclusion: We can take post-CCT ARR and PAC altogether into account to distinguish PA from EH, while caution should be taken to interpret CCT results with the suppression percentage of PAC. Post-CCT PAC may perform better to identify the unilateral than bilateral form of PA.

A novel CgIFNLP receptor involved in regulating ISG expression in oyster Crassostrea gigas.

Interferons (IFNs) are the key coordinators of antiviral immunity by binding to their receptors to orchestrate a complex transcriptional network in vertebrates. Recently, the existence of molluscan IFN-like system has been certified by the identification of important components in IFN system, such as IFN-like protein (CgIFNLP) from oyster Crassostrea gigas. In the present study, a novel CgIFNLP receptor (designed CgIFNLPR-1) was identified from C. gigas. The open reading frame (ORF) of CgIFNLPR-1 cDNA was of 1962 bp encoding a peptide of 653 amino acid residues with five fibronectin type III (FNIII) domains and one transmembrane helix region. The mRNA transcripts of CgIFNLPR-1 were constitutively distributed in all the tested tissues, with the highest level in gonad. After Poly (I:C) stimulation, the mRNA expression of CgIFNLPR-1 in haemocytes was significantly up-regulated to the highest level at 48 h (4.54-fold of that in control group, p < 0.05). CgIFNLPR-1 protein was mainly distributed in the cytoplasm and membrane of oyster haemocytes. CgIFNLP and CgIFNLPR-1 were able to interact with each other in vitro. After the CgIFNLPR-1 was knocked down by RNAi, the mRNA expression of IFN-stimulated genes (ISGs), including CgMx, CgViperin and CgIFNIP-44, were significantly inhibited after Poly (I:C) stimulation, which was 0.17, 0.31 and 0.53-fold of that in EGFP group, respectively (p < 0.01). These findings suggested that CgIFNLPR-1 was a novel CgIFNLP receptor in the oyster to recognize CgIFNLP and regulate the expressions of CgISGs.

Evaluation of the effects of glycated hemoglobin on cardiac function in patients with short-duration type 2 diabetes mellitus: A cardiovascular magnetic resonance study.

AIMS: To investigate the association between glycated hemoglobin (HbA1c) and myocardial dysfunction and to determine whether its association is independent of myocardial perfusion. METHODS: Sixty-four patients with type 2 diabetes mellitus (T2DM) were recruited. They were divided into groups according to their HbA1c level: the controlled T2DM group (HbA1c < 7%) and uncontrolled T2DM groups (HbA1c ≥ 7%). Meanwhile, 30 age-matched healthy volunteers were included. All patients with T2DM and healthy controls underwent cardiovascular magnetic resonance imaging to evaluate the myocardial mechanics and perfusion parameters. RESULTS: The circumferential and longitudinal peak strain (PS) (p = 0.009 and 0.002 respectively) and global radial, circumferential, and longitudinal peak strain diastolic strain rates (PDSRs) (p = 0.002, 0.001, and 0.001 respectively) were lower in the uncontrolled T2DM group than in the controls without diabetes. In multivariable linear regression analysis, HbA1c was independently related to all directions of the PS and PDSR. The myocardial perfusion parameters were not independently associated with the PS or PDSR. CONCLUSIONS: Cardiac function is impaired in Chinese T2DM patients with poor glucose control (HbA1c ≥ 7%), with preserved left ventricular (LV) ejection fraction, and disease duration <10 years. Poor blood glucose control is an independent predictor of LV myocardial dysfunction for patients with short-term T2DM.

Ammonia nitrogen exposure caused structural damages to gill mitochondria of clam Ruditapes philippinarum.

Ammonia nitrogen has been one of the key pollution indicators along the Chinese coastline for quite a few years. Our previous studies have proved that ammonia nitrogen is harmful for Ruditapes philippinarum clam in several aspects. Environmental concentrations of ammonia nitrogen were found to significantly decrease ATP contents and disturb ATP metabolism, in addition to reducing the potential across the mitochondrial membrane in clam gill tissues. Accordingly, mitochondrion is considered as one of the target organelles of ammonia nitrogen toxicity in clams. However, there is a lack of direct evidence to prove it. In order to reveal detail information of ammonia nitrogen toxicity on clam mitochondria and screen the related biomarker to indicate ammonia nitrogen pollution, mitochondrial parameters in gill tissues including swelling, mtDNA copy number and marker enzyme (succinic dehydrogenase, SDH) activity were measured after the clams were exposed to 0.1 mg/L and 0.5 mg/L ammonia nitrogen for 3 days and 21 days, respectively. Moreover, adverse effects of ammonia nitrogen exposure on clam mitochondrial ultra-structures, mitochondrial swelling and division were also discriminated under transmission electron microscope (TEM). Final results showed that ammonia nitrogen exposure to both concentrations significantly induced mitochondrial swelling, reduced the number of mitochondria and messed their normal structure, decreased the number of mtDNA copies and down-regulated SDH activity, all in a concentration and duration dependent manner. So, the present study helps us to better understand the structural damage of ammonia nitrogen on mitochondria in clam gill cells and provides fundamental data for ammonia nitrogen control in aquaculture.

The cGAS/STING-TBK1-IRF Regulatory Axis Orchestrates a Primitive Interferon-Like Antiviral Mechanism in Oyster.

Interferon (IFN) system is considered as the first defense line against viral infection, and it has been extensively studied in vertebrates from fish to mammals. In invertebrates, Vagos from arthropod and IFN-like protein (CgIFNLP) from Crassostrea gigas appeared to function as IFN-like antiviral cytokines. In the present study, the CgIFNLP protein in hemocytes was observed to increase after Poly (I:C) stimulation. After CgIFNLP was knocked down by RNAi, the mRNA expression of IFN-stimulated genes (CgISGs) was significantly inhibited. Both cyclic GMP-AMP synthase (CgcGAS) and stimulator of interferon gene (CgSTING) identified from oyster were able to recognize the double-stranded nucleic acid [Poly (I:C) and dsDNA] and expressed at high level after Poly (I:C) stimulation. The expression of CgIFNLP and interferon regulatory factors (CgIRF1/8) and the nuclear translocation of CgIRF8 were all suppressed in CgcGAS-RNAi or CgSTING-RNAi oysters after Poly (I:C) stimulation. The expression level of CgSTING and TANK binding kinase1 (CgTBK1) did not decrease in CgcGAS-RNAi oysters. After CgSTING was knocked down, the high expression of CgTBK1 induced by Poly (I:C) was prevented significantly. These results indicated that there was a primitive IFN-like antiviral mechanism dependent on the cGAS/STING-TBK1-IRFs regulatory axis in mollusks, which was different from the classic cGAS-STING-TBK1 signal pathway in mammals.