Transcriptomic analysis of the hypoxia-inducible factor 1α impact on the gene expression profile of chicken fibroblasts under hypoxia.

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional regulator that mediates cellular adaptive responses to hypoxia. Hypoxia-inducible factor 1α (HIF-1α) is involved in the development of ascites syndrome (AS) in broiler chickens. Therefore, studying the effect of HIF-1α on the cellular transcriptome under hypoxic conditions will help to better understand the mechanism of HIF-1α in the development of AS in broilers. In this study, we analyzed the gene expression profile of the chicken fibroblast cell line (DF-1) under hypoxic conditions by RNA-seq. Additionally, we constructed the HIF-1α knockdown DF-1 cell line by using the RNAi method and analyzed the gene expression profile under hypoxic conditions. The results showed that exposure to hypoxia for 48 h had a significant impact on the expression of genes in the DF-1 cell line, which related to cell proliferation, stress response, and apoptosis. In addition, after HIF-1α knockdown more differential expression genes appeared than in wild-type cells, and the expression of most hypoxia-related genes was either down-regulated or remained unchanged. Pathway analysis results showed that differentially expressed genes were mainly enriched in pathways related to cell proliferation, apoptosis, and oxidative phosphorylation. Our study obtained transcriptomic data from chicken fibroblasts at different hypoxic times and identified the potential regulatory network associated with HIF-1α. This data provides valuable support for understanding the transcriptional regulatory mechanism of HIF-1α in the development of AS in broilers.

Oligodendrocyte progenitor cell-specific delivery of lipid nanoparticles loaded with Olig2 synthetically modified messenger RNA for ischemic stroke therapy.

The transcription factor Olig2 is highly expressed throughout oligodendroglial development and is needed for the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and remyelination. Although Olig2 overexpression in OPCs is a possible therapeutic target for enhancing myelin repair in ischemic stroke, achieving Olig2 overexpression in vivo remains a formidable technological challenge. To address this challenge, we employed lipid nanoparticle (LNP)-mediated delivery of Olig2 synthetically modified messenger RNA (mRNA) as a viable method for in vivo Olih2 protein overexpression. Specifically, we developed CD140a-targeted LNPs loaded with Olig2 mRNA (C-Olig2) to achieve targeted Olig2 protein expression within PDGFRα+ OPCs, with the goal of promoting remyelination for ischemic stroke therapy. We show that C-Olig2 promotes the differentiation of PDGFRα+ OPCs derived from mouse neural stem cells into mature oligodendrocytes in vitro, suggesting that mRNA-mediated Olig2 overexpression is a rational approach to promote oligodendrocyte differentiation and remyelination. Furthermore, when C-Olig2 was administered to a murine model of ischemic stroke, it led to improvements in blood‒brain barrier (BBB) integrity, enhanced remyelination, and rescued learning and cognitive deficits. Our comprehensive analysis, which included bulk RNA sequencing (RNA-seq) and single-nucleus RNA-seq (snRNA-seq), revealed upregulated biological processes related to learning and memory in the brains of mice treated with C-Olig2 compared to those receiving empty LNPs (Mock). Collectively, our findings highlight the therapeutic potential of multifunctional nanomedicine targeting mRNA expression for ischemic stroke and suggest that this approach holds promise for addressing various brain diseases. STATEMENT OF SIGNIFICANCE: While Olig2 overexpression in OPCs represents a promising therapeutic avenue for enhancing remyelination in ischemic stroke, in vivo strategies for achieving Olig2 expression pose considerable technological challenges. The delivery of mRNA via lipid nanoparticles is considered aa viable approach for in vivo protein expression. In this study, we engineered CD140a-targeted LNPs loaded with Olig2 mRNA (C-Olig2) with the aim of achieving specific Olig2 overexpression in mouse OPCs. Our findings demonstrate that C-Olig2 promotes the differentiation of OPCs into oligodendrocytes in vitro, providing evidence that mRNA-mediated Olig2 overexpression is a rational strategy to foster remyelination. Furthermore, the intravenous administration of C-Olig2 into a murine model of ischemic stroke not only improved blood-brain barrier integrity but also enhanced remyelination and mitigated learning and cognitive deficits. These results underscore the promising therapeutic potential of multifunctional nanomedicine targeting mRNA expression in the context of ischemic stroke.

Molecular characterization of Blastocystis spp. in Hotan Black chickens in southern Xinjiang.

To determine the infection status and assess the zoonotic potential of Blastocystis spp. in Hotan Black chickens in southern Xinjiang, China, fecal samples were collected from 617 chickens on 18 large-scale farms. The presence of Blastocystis spp. was determined using polymerase chain reaction based on the small subunit rRNA (SSU rRNA) locus. The results revealed an overall infection rate of 26.3% (162/617). Samples from Farm 1 in Luopu County showed the highest infection rate (76.3%, 29/38). The highest and lowest infection rates were detected in the <30-day (34.4%, 43/125) and > 90-day age groups (12.4%, 11/89), respectively. The infection rate decreased with increasing age. Statistical analysis showed significant differences in the infection rates of Blastocystis spp. among the different sampling sites (p < 0.05) and age groups (p < 0.05). Four Blastocystis spp. subtypes (ST6, ST7, ST10, and ST23) were identified. The infection rates of the zoonotic subtypes, ST6 and ST7, were 3.2% (20/617) and 22.2% (137/617), respectively. The presence of Blastocystis spp. and zoonotic subtypes provided evidence for the potential transmission of this pathogen between Hotan Black chickens and humans, especially in animal handlers in this area.

Systemic meta-analysis: apigenin's effects on lung inflammation and oxidative stress.

OBJECTIVE: This study aimed to investigate the potential anti-inflammatory and antioxidant effects of apigenin in rats with acute lung injury (ALI). We also examined changes in levels of inflammatory and antioxidant factors after apigenin treatment in a rat model of ALI.Methods: We searched several databases, including PubMed, Scopus, EMBASE, Web of Science, ProQuest, and GoogleScholar, to retrieve relevant articles for our systematic review and meta-analysis.Five studies with 226 rat models of ALI were included in this study. We investigated inflammatory factors and oxidative stress with the corresponding 95% confidence interval in three groups: 1. Group1 (control vs. ALI), 2. Group2 (ALI vs. apigenin10), and 3. Group3 (ALI vs. apigenin20). RESULTS: Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (ALI), compared with that in the control group, respectively (correlation: 0.194; 95% confidence intervals, 0.101-0.282, p value = .001, z-value= 4.08) and (correlation: 0.099; 95% confidence intervals, 0.016-0.182, p value = .020, z value= 2.325). Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (apigenin 10 mg/kg), compared with that in the control group (ALI), respectively (correlation: 0.476; 95% confidence intervals, 0.391-0.553, p value = .001, z-value= 9.678) and (correlation: 0.415; 95% confidence intervals, 0.313-0.508, p value= .001, z-value= 7.349). CONCLUSION: Apigenin may have potential anti-inflammatory and antioxidant effects in rat models of ALI. However, the efficacy of apigenin as a therapeutic strategy requires further investigation through prospective controlled randomized trials.

Dominant infection of Cryptosporidium baileyi in broiler chickens in Zhejiang Province, China.

Cryptosporidium is a common enteric parasite in chickens. A total of 812 fecal specimens were collected from 11 broiler farms in Zhejiang Province, China, and analyzed by nested PCR amplification based on the small subunit ribosomal RNA (SSU rRNA) gene. The overall infection rate of Cryptosporidium was 6.3% (51/812), and five of 11 farms were Cryptosporidium positive. Broilers aged > 90 days accounted for the highest infection rate of 16.1% (6/56), followed by those aged 30-60 days (10.6%, 38/358) and 60-90 days (4/378, 1.1%). Two Cryptosporidium species were identified by sequence analysis, with the predominant species being C. baileyi (96.1%, 49/51) and the minor infection being C. meleagridis (3.9%, 2/51). Based on the 60-kDa glycoprotein (gp60) gene, two C. meleagridis-positive isolates were identified as one known subtype, IIIbA24G1R1. This study indicated the common occurrence of C. baileyi in broiler chickens in this region and low zoonotic transmission potential of Cryptosporidium to humans.

ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer.

BACKGROUND: Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq. METHODS: A total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed. RESULTS: The results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence. CONCLUSIONS: The significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role.

GABAergic signaling abnormalities in a novel CLU mutation Alzheimer's disease mouse model.

The CLU rs11136000C mutation (CLUC) is the third most common risk factor for Alzheimer's disease (AD). However, the mechanism by which CLUC leads to abnormal GABAergic signaling in AD is unclear. To address this question, this study establishes the first chimeric mouse model of CLUC AD. Examination of grafted CLUC medial ganglionic eminence progenitors (CLUC hiMGEs) revealed increased GAD65/67 and a high frequency of spontaneous releasing events. CLUC hiMGEs also impaired cognition in chimeric mice and caused AD-related pathologies. The expression of GABA A receptor, subunit alpha 2 (Gabrα2) was higher in chimeric mice. Interestingly, cognitive impairment in chimeric mice was reversed by treatment with pentylenetetrazole, which is a GABA A receptor inhibitor. Taken together, these findings shed light on the pathogenesis of CLUC AD using a novel humanized animal model and suggest sphingolipid signaling over-activation as a potential mechanism of GABAergic signaling disorder.

Clinical characteristics of venous thromboembolism onset from severe high altitude pulmonary edema in plateau regions.

BACKGROUND: To investigate venous thromboembolism (VTE) in hospitalized patients with severe high altitude pulmonary edema (HAPE), we performed a single center retrospective study to evaluate its clinical characteristics, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center in plateau regions. METHODS: We studied a total of 18 patients with severe HAPE from January 1, 2012 to December 31, 2021. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities and cardiac ultrasound, and computed tomographic pulmonary angiography (CTPA) variables were obtained, and comparisons were made between groups with and without VTE. RESULTS: Of the 18 patients hospitalized with severe HAPE (age 43 (range, 34-54) years, 14 [77.8%] men), 7 patients developed VTE (38.9%), including 5 with deep vein thrombosis (DVT) and pulmonary embolism (PE), 2 of whom had DVT only. Eighteen patients are all firstly rapid ascent to high altitudes which the mean altitude was 3700 m (3656-4050 m). Compared with patients who did not have VTE, patients with VTE had a longer time in hospital (13 [11, 19] versus 9 [7, 12]; P = 0.027), respiratory failure (6 [85.7%] versus 2 [18.2%]; P = 0.013), the shortened APTT (21.50 [19.00, 27.50] versus 26.30 [24.80, 30.10]; P = 0.044) and the higher level of D-dimer (7.81 [4.62, 9.60] versus 2.90 [1.75, 3.37]; P = 0.003). The proportion of thromboprophylaxis is too low in our cohort which 2 of 18 (11.1%) patients were given VTE prophylaxis. There was no statistically significant difference between the VTE and non-VTE groups (0 [0.0%] versus 2 [18.2%]; P = 0.497). CONCLUSIONS: The prevalence of VTE is high in hospitalized patients with severe high altitude pulmonary edema (HAPE). Prophylaxis for venous thromboembolism may be protective in severe HAPE patients after admission. Our data seem to suggest that VTE is probably an additional prognostic factors in patients with severe HAPE.

Myeloperoxidase in the pericardial fluid improves the performance of prediction rules for postoperative atrial fibrillation.

OBJECTIVES: After surgery, inflammation is a prominent factor influencing postoperative atrial fibrillation. Myeloperoxidase is a major contributor to inflammatory responses after surgical tissue damage. We evaluated whether myeloperoxidase is associated with postoperative atrial fibrillation clinically and in an animal model. METHODS: This prospective cohort study included patients undergoing isolated coronary artery bypass grafting. Myeloperoxidase concentrations in blood and pericardial fluid were determined at baseline and 6, 12, and 18 hours after coronary artery bypass grafting. Myeloperoxidase activity in blood, pericardial fluid, and atrium were also evaluated in a canine coronary artery bypass grafting model. Electrophysiologic, histologic, and immunohistochemistry analyses were performed to explore underlying mechanisms. RESULTS: Postoperative atrial fibrillation occurred in 45 of 137 patients (32.8%). Patients with postoperative atrial fibrillation had significantly higher serum and pericardial myeloperoxidase levels. Individual clinical and surgical factors had moderate predictive value (area under the curve, 0.760) for postoperative atrial fibrillation. Discrimination improved remarkably when myeloperoxidase was combined with other parameters (area under the curve, 0.901). Pericardial myeloperoxidase at 6 hours postoperatively was the strongest independent predictor of postoperative atrial fibrillation (odds ratio, 19.215). The rate of postoperative atrial fibrillation increased exponentially across pericardial myeloperoxidase grades. Compared with controls, coronary artery bypass grafting-treated dogs showed higher atrial fibrillation vulnerability and maintenance, shorter atrial effective refractory period, attenuated connexin 43 expression, and increased myocardial and pericardial myeloperoxidase activity. Connexin 43 expression and atrial effective refractory period were strongly negatively correlated with myocardial and pericardial myeloperoxidase activity. CONCLUSIONS: Myeloperoxidase is linked to postoperative atrial fibrillation, and the ability to predict postoperative atrial fibrillation was remarkably improved by adding pericardial myeloperoxidase. Myeloperoxidase-related atrial structural and electrical remodeling is a physiologic substrate for this arrhythmia.

Sustained ameliorating effects and autonomic mechanisms of transcutaneous electrical acustimulation at ST36 in patients with chronic constipation.

Background and aims: The treatment of chronic constipation is still a great challenge in clinical practice. This study aimed to determine the efficacy and sustained effects of transcutaneous electrical acustimulation (TEA) at acupoint ST36 on the treatment of chronic constipation and explore possible underlying mechanisms. Methods: Forty-four patients with chronic constipation were recruited and randomly assigned to a TEA group or sham-TEA group. A bowel diary was recorded by the patients. The Patient Assessment of Constipation Symptom (PAC-SYM) and the Patient Assessment of Constipation Quality of Life (PAC-QoL) questionnaires were administered during each visit. Anal and rectal functions were evaluated with anorectal manometry. Autonomic functions were assessed by the special analysis of heart rate variability derived from the ECG recording. Results: Compared with sham-TEA, 2-week TEA treatment significantly increased the number of spontaneous bowel movements (SBMs) (5.64 ± 0.54 vs. 2.82 ± 0.36, P < 0.001) and lowered the total scores of PAC-SYM (0.90 ± 0.14 vs. 1.35 ± 0.13, P < 0.001) and PAC-QoL (0.89 ± 0.13 vs. 1.32 ± 0.14, P < 0.05). TEA improved symptoms, as reflected by a reduction in the straining (P < 0.001), the incomplete defecation (P < 0.05), the frequency of emergency drug use (P < 0.05), the days of abdominal distension (P < 0.01) and an increase in intestinal satisfaction (P < 0.01). Interestingly, the effects of TEA on the improvement of weekly SBMs sustained four weeks after the cessation of treatment (P < 0.001). Anorectal manometry indicated that 2-week treatment of TEA lowered the threshold of first sensation (P < 0.05), desire of defecation (P < 0.01) and maximum tolerable volume (P < 0.001) compared with sham-TEA group. TEA also significantly enhanced vagal activity, reflected by high-frequency band of heart rate variability, compared with sham-TEA (57.86 ± 1.83 vs. 48.51 ± 2.04, P < 0.01). Conclusion: TEA ameliorates constipation with sustained effects, which may be mediated via improvement of rectal sensitivity and enhancement of vagal activity. Clinical trial registration: [https://clinicaltrials.gov/], identifier [ChiCTR210004267].

Genetic characterization of Cryptosporidium spp. in Hotan Black Chickens in China reveals two novel subtypes of Cryptosporidium meleagridis.

A total of 617 fecal specimens were collected on 18 Hotan Black chicken farms in Southern Xinjiang, China, and tested for the presence of Cryptosporidium spp. by PCR of the small subunit ribosomal RNA (SSU rRNA) gene. The overall infection rate by Cryptosporidium spp. was 11.5% (71/617), and ten of the 18 farms were positive. The infection rate by Cryptosporidium spp. was 14.5% (48/331) in the 30-60 d group, higher than chickens in the <30 d (12.0%, 15/125), 60-90 d (6.9%, 5/72), and >90 d (3.4%, 3/89) groups. Cryptosporidium meleagridis (n = 38) and C. baileyi (n = 33) were confirmed by sequencing analysis. A total of 25 of the 38 C. meleagridis-positive specimens were subtyped successfully at the gp60 gene, including one known subtype (IIIbA23G1R1, n = 1) and two novel subtypes, named IIIbA25G1R1 (n = 20) and IIIbA31G1R1 (n = 4). The results showed that infection by Cryptosporidium spp. in Hotan Black Chickens was common in this area and the distribution of C. meleagridis subtypes had regional characteristics.

Title: La caractérisation génétique de Cryptosporidium spp. chez les poulets noirs du Hotan en Chine révèle deux nouveaux sous-types de Cryptosporidium meleagridis. Abstract: Un total de 617 échantillons fécaux ont été prélevés dans 18 élevages de poulets noirs du Hotan dans le sud du Xinjiang, en Chine, et testés pour la présence de Cryptosporidium spp. par PCR du gène de la petite sous-unité de l'ARN ribosomique (ARNr SSU). Le taux d'infection global par Cryptosporidium spp. était de 11,5 % (71/617) et dix des 18 élevages étaient positifs. Le taux d'infection de Cryptosporidium spp. était de 14,5 % (48/331) dans le groupe 30­60 jours, supérieur à celui des poulets dans les groupes <30 jours (12,0 %, 15/125), 60­90 jours (6,9 %, 5/72) et >90 jours (3,4 %, 3/89). Cryptosporidium meleagridis (n = 38) et C. baileyi (n = 33) ont été confirmés par analyse de séquençage. Vingt-cinq des 38 spécimens positifs pour C. meleagridis ont été sous-typés avec succès au niveau du gène gp60, dont un sous-type connu (IIIbA23G1R1, n = 1) et deux nouveaux sous-types, nommés IIIbA25G1R1 (n = 20) et IIIbA31G1R1 (n = 4). Les résultats ont montré que l'infection par Cryptosporidium spp. chez les poulets noirs du Hotan était commune dans cette zone et que la distribution des sous-types de C. meleagridis avait des caractéristiques régionales.

Longitudinal surveillance of Cryptosporidium spp. in broiler chickens in Xinjiang, northwest China: genetic diversity of Cryptosporidium meleagridis subtypes.

Cryptosporidium spp. are common enteric parasites in humans and animals. Herein, 175 faecal specimens were collected from a broiler farm in Xinjiang, China, including seven repeated samplings at 10-day intervals of broilers aged 10 to 70 days. Cryptosporidium was detected and identified by PCR-RFLP analysis. The overall infection rate of Cryptosporidium in broilers was 23.4% (41/175), with the highest infection rate of 48.0% (12/25) at 40 days of age, and no infection was detected at 10 days of age. Two Cryptosporidium species were confirmed, namely, C. baileyi (3.4%, 6/175) and C. meleagridis (20%, 35/175). In total, 21 of 35 C. meleagridis isolates were successfully subtyped based on the gp60 gene, and one known subtype, IIIgA22G3R1 (n = 1), and three novel subtypes, IIIbA25G1R1 (n = 10), IIIgA24G3R1 (n = 9) and IIIgA25G2R1 (n = 1), were identified. Our findings highlight the genetic diversity of C. meleagridis in Xinjiang and the potential endemic characteristics of the subtypes.

Projected Losses of Ecosystem Services Incurred by Reserve Resources of Cultivated Land Development and Development Priority: A Case Study of Linzhou City in Henan Province, China.

The development of reserve resources of cultivated land (RRCL) is a vital way of supplementing cultivated land, and plays a crucial role in ensuring food security. However, if we blindly pursue the quantity of development while ignoring the conservation of the ecosystem, we are likely to waste land resources and destroy the ecological environment. Therefore, it is necessary to address the urgent issue of preventing ecological risks resulting from the development of RRCL and to enhance the actual effect of supplementing cultivated land. Taking Linzhou City in Henan Province as an example, this paper first assessed the tillability of RRCL and estimated the functionality of ecosystem services. Then it projected the losses of ecosystem services incurred by RRCL development, based on which it determined the development priority. The following conclusions were drawn: (1) The total area of RRCL in Linzhou City amounts to 8845 hectares. (2) According to the research forecast, the total annual losses of ecosystem services incurred by RRCL development in Linzhou City include: water conservation of 776,200 m3, soil retention of 340.84 t, and carbon sequestration and oxygen release of 2311.12 t. Moreover, the total value of losses amounts to RMB 15.7754 million. (3) The ecological losses incurred by RRCL development vary with the different types of land. Overall, the ecological loss derived from reclaimable land is inferior to that of cultivable land, with the average value of ecological loss amounting to RMB 600 and RMB 5300 per hectare, respectively. The ecological loss from the development of class II land is: pond < garden land < artificial grassland < artificial forest land < natural grassland < bare land. Moreover, land development should be postponed when the quantity of ecological losses reaches level III or higher. (4) Corrections are made based on the ecological coefficient of the economic potential of RRCL development so as to determine the priority of development. The research findings indicate that the priority of development of eastern towns is higher than that of central and western towns in Linzhou City, with Donggang and Hengshui topping the priority list and Shibanyan, Lingyang, and Chengguan having the lowest priority.

Expression profile analysis of sheep ovary after superovulation and estrus synchronisation treatment.

Superovulation is a widely used reproductive technique in livestock production, but the mechanism of sheep's superovulation is not yet clear. Here, a method of superovulation and estrus synchronisation was used to treat female Duolang sheep. After treatment, there were significant differences in serum FSH and LH levels and the number of dominant follicles between the two groups of sheep. We identified a total of 5021 differentially expressed genes (11, 13 and 15 days after treatment) and performed RT-qPCR analysis to identify several mRNA expression levels. GO and KEGG enrichment analysis revealed that differentially expressed genes were involved in the regulation of signalling pathways of follicular development, cell cycle, material synthesis, energy metabolism, such as COL3A1, RPS8, ACTA2, RPL7 RPS6 and TNFAIP6 may play a key role in regulating the development of follicles. Our results show a comprehensive expression profile after superovulation and estrus synchronisation treatment. We provide the basis for further research on breeding techniques to improve the ovulation rate and birth rate of livestock.

Inclusion of interleukin-6 improved performance of postoperative delirium prediction for patients undergoing coronary artery bypass graft (POD-CABG): A derivation and validation study.

BACKGROUND: Patients undergoing coronary artery bypass graft (CABG) are at high risk for developing postoperative delirium (POD). A simple prediction rule may benefit patients from early identification of POD followed by adequate preventive strategies. The purpose of the current study was to develop and validate a POD prediction rule for patients undergoing CABG (POD-CABG), by considering all possible perioperative factors. METHODS: In this prospective cohort study, patients who underwent first elective isolated CABG were continuously enrolled from May 2014 to November 2015 in a tertiary hospital. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Patients' perioperative risk factors were collected through interviews and review of medical records. The area under receiver-operating characteristic curve (AUC) was used to assess the overall performance of the predictive rule. RESULTS: A total of 242 and 148 patients were enrolled in the derivation and validation cohorts, respectively. Multiple logistic regression analysis identified seven variables that were independently associated with POD: age (≥65 years), gender (female), history of myocardial infarction and diabetes mellitus, postoperative atrial fibrillation, the use of intra-aortic balloon pump, and serum interleukin-6 ≥478 pg/ml at 18 hours after surgery. The AUC of the POD-CABG was 0.84 (95% CI, 0.79-0.90) in the derivation cohort, and was 0.86 (95% CI, 0.80-0.91) after bootstrap resampling. The AUC was 0.81 (95% CI, 0.73-0.88) after the POD-CABG was applied to the validation cohort. CONCLUSIONS: The POD-CABG with inclusion of interleukin-6 demonstrated good performance in predicting POD.

A Prediction Rule Including Interleukin-6 in Pericardial Drainage Improves Prediction of New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting.

OBJECTIVE: To test the hypothesis that a prediction rule including levels of interleukin-6 in pericardial drainage (pdIL-6) would improve the discrimination in classifying patients undergoing coronary artery bypass grafting (CABG) into different postoperative atrial fibrillation (POAF) risk levels. DESIGN: Prospective cohort study. SETTING: A university-affiliated tertiary hospital. PARTICIPANTS: Patients undergoing CABG. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We prospectively recruited patients who underwent CABG into derivation and validation cohorts. The independent predictors were identified in the derivation cohort using multiple logistic regression and tested in the validation cohort. The performance of the predictive model was tested using area under the receiver operating characteristic curve (AUC) in both cohorts. A prediction rule was created by assigning points to each predictor. Patients were classified in various risk levels according to their total risk scores. We enrolled 302 and 207 patients in the derivation and validation cohorts, respectively. Multiple logistic regression analysis identified six predictors: age ≥61 y, left atrial diameter ≥49 mm, right atrial diameter ≥45 mm, number of grafts ≥3, and serum uric acid ≥226 µmol/L and pdIL-6 levels ≥166 ng/mL at postoperative 12 h. The AUC of the model was 0.78 and 0.77 for the derivation and validation cohort, respectively, which was greatly increased by adding pdIL-6. Patients were stratified into low-risk, moderate-risk and high-risk groups. CONCLUSIONS: A POAF prediction rule including pdIL-6 had good performance for stratifying CABG patients into various risk groups for POAF. The inclusion of pdIL-6 resulted in clinically meaningful improvement in risk prediction.

Trade-Off and Projecting Effects of Land Use Change on Ecosystem Services under Different Policies Scenarios: A Case Study in Central China.

Predicting the spatio-temporal evolution characteristics and trade-off/synergy relationships of ecosystem service value (ESV) under different policy scenarios is of great significance for realizing regional sustainable development. This study established a framework and used the geographical simulation and optimization systems-future land use simulation (GeoSOS-FLUS) model and bivariate local autocorrelation analysis to stimulate and predict the impact of land use change on the ESV of Anyang City from 1995 to 2025. We also explored the trade-offs and synergy among ecosystem services under three policy scenarios (natural evolution, cultivated land protection, and ecological protection) in 2025. Results show that (1) the land use change in Anyang from 1995 to 2025 was significant, and the degree of land use change under the cultivated land and ecological protection scenarios was more moderate than that under the natural evolution scenario; (2) The total ESV decreased between 1995 and 2015, amounting to losses of 1126 million yuan, and the decline from 2015 to 2025 under the natural evolution scenario was more significant than those under the cultivated land protection and ecological protection scenarios; and (3) an obvious synergy was observed between various ecosystem services in Anyang City under different scenarios in 2025, and the most significant synergy was observed under the natural evolution scenario. In terms of spatial distribution, the agglomeration of "high-high" synergy in the west and "low-low" synergy in the central region was significant. Local areas showed "high-low" and "low-high" trade-off relationships scattered between their built land and woodland or cultivated land. The proposed framework can provide certain scientific support for regulating land use and ecosystem services in rapidly urbanized areas.

Interleukin-6 Receptor Asp358 A>C Polymorphism Is Associated With Postoperative Atrial Fibrillation.

BACKGROUND: This study examined the associations of single-nucleotide polymorphisms in the interleukin-6 receptor gene (Asp358 A>C) and the interleukin-6 promoter (-174G>C and -597G>A) with interleukin-6 levels and postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). METHODS: The study enrolled 371 Chinese Han patients who were undergoing CABG. Serum interleukin-6 levels were measured preoperatively and at 6, 12, and 18 hours postoperatively. Genotypes for the 3 polymorphisms were determined. RESULTS: Overall, POAF developed in 30.2% of patients. The CC genotype and C allele frequencies for the interleukin-6 receptor Asp358 A>C polymorphism were significantly higher in patients with POAF than in patients without POAF (P = .003), and the interleukin-6 levels were significantly higher in patients with the CC genotype compared with A allele carriers at 6, 12, and 18 hours in the overall cohort and at 12 and 18 hours in the POAF subgroup, but there were no significant differences in the non-POAF subgroup. However, the allele and genotype frequencies of the interleukin-6 -174G>C and -597G>A polymorphisms were similar among groups, and there were no differences in interleukin-6 levels at any time point between the C/A allele carriers and the patients with GG genotypes. Univariate analysis showed that the CC genotype for interleukin-6 receptor Asp358 A>C, age, and history of cerebrovascular disease were associated with POAF. Multivariable regression showed that the CC genotype was independently related to the development of POAF (odds ratio, 2.01; 95% confidence interval: 1.15 to 3.52; P = .014). CONCLUSIONS: The interleukin-6 receptor Asp358 A>C polymorphism may contribute to genetic susceptibility to POAF after CABG.

Change in Serum Level of Interleukin 6 and Delirium After Coronary Artery Bypass Graft.

BACKGROUND: Serum level of interleukin 6 (IL-6) is known to be associated with postoperative delirium. However, no consensus has emerged on the postoperative time point at which IL-6 level may predict postoperative delirium after coronary artery bypass graft surgery. OBJECTIVES: To compare trends in IL-6 levels in patients with and without postoperative delirium and to examine the relationship between IL-6 levels at different times and postoperative delirium after coronary artery bypass graft. METHODS: A prospective cohort study of patients who underwent their first elective isolated coronary artery bypass graft between November 2013 and August 2015 at a cardiac intensive care unit in Beijing, China. Concentrations of IL-6 were measured before the operation and at the 6th, 12th, and 18th postoperative hours. Participants were assessed for postoperative delirium twice daily for 5 days. Univariate and multivariate logistic regression analyses were done to determine associations between IL-6 levels at different time points, postoperative changes in IL-6 levels, and the occurrence of postoperative delirium. RESULTS: Postoperative delirium was diagnosed in 85 of 266 patients (32%). Levels of IL-6 were significantly higher in patients with postoperative delirium than in patients without it at the 6th, 12th, and 18th postoperative hours (P = .03, .004, and .001, respectively). Change in IL-6 level (odds ratio, 2.97; 95% CI, 1.20-7.31; P = .02) and IL-6 level of 583 pg/mL or higher at the 18th postoperative hour (odds ratio, 5.20; 95% CI, 1.84-14.70; P = .002) were associated with higher incidence of postoperative delirium. CONCLUSION: Interleukin 6 level (≥ 583 pg/mL) at the 18th postoperative hour may serve as a potent predictor of postoperative delirium in coronary artery bypass graft patients.