MiR-411-5p Promotes Vascular Smooth Muscle Cell Phenotype Switch by Inhibiting Expression of Calmodulin Regulated Spectrin-Associated Protein-1.

When stimulated, vascular smooth muscle cells (VSMCs) change from a differentiated to a dedifferentiated phenotype. Dedifferentiated VSMCs have a key activity in cardiovascular diseases such as in-stent restenosis. MicroRNAs (miRNAs) have crucial functions in conversion of differentiated VSMCs to a dedifferentiated phenotype. We investigated the activity of miR-411-5p in the proliferation, migration, and phenotype switch of rat VSMCs.Based on a microRNA array assay, miR-411-5p expression was found to be significantly increased in cultured VSMCs stimulated by platelet-derived growth factor-BB (PDGF-BB). A CCK-8 assay, transwell assay, and scratch test were performed to measure the effect of miR-411-5p on the proliferation and migration of PDGF-BB-treated VSMCs. MiR-411-5p promoted expression of dedifferentiated phenotype markers such as osteopontin and tropomyosin 4 in PDGF-BB-treated VSMCs. Using mimics and inhibitors, we identified the target of miR-411-5p in PDGF-BB-treated VSMCs and found that calmodulin-regulated spectrin-associated protein-1 (CAMSAP1) was involved in the phenotypic switch mediated by PDGF-BB.By inhibiting expression of CAMSAP1, miR-411-5p enhanced the proliferation, migration, and phenotype switch of VSMCs.Blockade of miR-411-5p interaction with CAMSAP1 is a promising approach to treat in-stent restenosis.

Red Blood Cell Distribution Width to Albumin Ratio for Predicting Type I Cardiorenal Syndrome in Patients with Acute Myocardial Infarction: A Retrospective Cohort Study.

Purpose: Red blood cell distribution width to albumin ratio (RAR) is a novel inflammatory biomarker that independently predicts adverse cardiovascular events and acute kidney injury. This study aimed to assess the predictive value of RAR for cardio-renal syndrome type I (CRS-I) risk in acute myocardial infarction (AMI) patients. Patients and methods: This study retrospectively enrolled 551 patients who were definitively diagnosed as AMI between October 2021 and October 2022 at the Affiliated Zhongda Hospital of Southeast University. Participants were divided into two and four groups based on the occurrence of CRS-I and the quartiles of RAR, respectively. Demographic data, laboratory findings, coronary angiography data, and drug utilization were compared among the groups. Logistic regression and receiver operating characteristic curve (ROC) analysis were performed to identify independent risk factors for CRS-I and evaluated the predictive value of RAR for CRS-I. Results: Among the cohort of 551 patients, 103 (18.7%) developed CRS-I. Patients with CRS-I exhibited significantly elevated RAR levels compared to those without the condition, and the incidence of CRS-I correlated with escalating RAR. Univariate and multivariate logistic regression analyses identified RAR as an independent risk factor for CRS-I. ROC curves analysis demonstrated that RAR alone predicted CRS-I with an area under the curve (AUC) of 0.683 (95% CI=0.642-0.741), which was superior to the traditional inflammatory marker C-reactive protein (CRP). Adding the variable RAR to the model for predicting the risk of CRS-I further improved the predictive value of the model from 0.808 (95% CI=0.781-0.834) to 0.825 (95% CI=0.799-0.850). Conclusion: RAR is an independent risk factor for CRS-I, and high levels of RAR are associated with an increased incidence of CRS-I in patients with AMI. RAR emerges as a valuable and readily accessible inflammatory biomarker that may play a pivotal role in risk stratification in clinical practice.

Marijuana Use May Be Associated with Reduced Prevalence of Prostate Cancer: A National Survey on Drug Use and Health Study from United States of America.

Preclinical evidence indicates the potential anti-tumor capabilities of cannabinoids in prostate cancer (PC). We undertook a cross-sectional study using National Survey on Drug Use and Health data from 2002 to 2020, involving 2503 participants in the USA. The independent variable was marijuana use status (current, former, never), while the dependent variable was self-reported PC (yes, no). Eleven other demographic variables were assessed as covariates. PC prevalence was lower among current marijuana users (46/145, 31.7%) and former users (323/1021, 31.6%) compared to non-users (534/1337, 39.9%, p < 0.001). PC prevalence was lower among users versus non-users in the elderly (≥65) (36.4% vs. 42.4%, p = 0.016) and non-Hispanic white subgroups (28.9% vs. 38.3%, p < 0.001). There were no significant PC prevalence differences between users and non-users in the younger population (50-64) or other race/ethnicity. In the multivariable analyses, former marijuana use was associated with lower PC compared to never using (odd ratio = 0.74, 95% CI 0.62-0.90, p = 0.001). Current use was also suggestive of reduced prevalence but was not statistically significant (odd ratio = 0.77, 95% CI 0.52-1.14, p = 0.198), possibly due to low sample size. Our findings from a large national survey provide additional data to link marijuana use with lower PC prevalence.

The relationship between perioperative serum albumin and contrast-induced acute kidney injury in patients after percutaneous coronary intervention.

OBJECTIVE: Contrast-induced acute kidney injury (CI-AKI) is a common complication in patients undergoing percutaneous coronary intervention (PCI). Studies have shown that perioperative serum albumin levels may play a role in the occurrence of CI-AKI. In this study, we aimed to investigate the effect of perioperative serum albumin (delta albumin or &Alb) levels on the occurrence and long-term prognosis of CI-AKI patients after PCI. METHODS: A total of 959 patients who underwent PCI between January 2017 and January 2019 were selected for this study. A receiver operating characteristic curve was used to determine the optimal cut-off value of the &Alb level for predicting CI-AKI after PCI. Patients were divided into two groups based on the optimal cut-off value: the high &Alb group (&Alb ≥ 4.55 g/L) and the control group (&Alb < 4.55 g/L). The incidences of CI-AKI and major adverse cardiac events (MACEs, including all-cause death, nonfatal myocardial infarction, and target vessel revascularization) were compared between the groups. Cox regression analysis was used to identify predictors of long-term prognosis after PCI. RESULTS: Of the 959 patients, 147 (15.3%) developed CI-AKI after PCI. The CI-AKI group had a greater level of &Alb than did the non-CI-AKI group [(6.14 (3.90-9.10) versus 3.48 (4.31-6.57), P < 0.01)]. The incidence of CI-AKI in the high &Alb group was significantly greater than that in the low group (23.6% versus 8.3%, P < 0.01). After a 1-year follow-up, the incidence of MACEs was significantly greater in the high &Alb group than in the low group (18.6% versus 14.5%, P = 0.030). Cox regression analysis confirmed that CI-AKI was an independent predictor of MACEs at the 1-year follow-up (HR 1.43, 95% CI 1.04-1.96, P = 0.028). In addition, patients with low preoperative serum albumin levels had s significantly greater incidence of MACEs than did those with high preoperative serum albumin levels (23.2% versus 19.5%, P = 0.013). CONCLUSION: In summary, high baseline &Alb levels are an independent risk factor for CI-AKI in patients after PCI. The occurrence of CI-AKI in the perioperative period is also an independent predictor of long-term prognosis after PCI. These findings highlight the importance of monitoring &Alb levels and taking steps to prevent CI-AKI in patients undergoing PCI.

C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability.

Complement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors. Importantly, the excitation and inhibition of mPFC neurons have opposing effects on depressive-like behaviors, aligning with increased and decreased excitability by C3aR deletion and activation in cortical neurons. In particular, inhibiting mPFC glutamatergic (mPFCGlu) neurons, the main neuronal subpopulation expresses C3aR, induces depressive-like behaviors in saline-treated WT and KO mice, but not in LPS-treated KO mice. Compared to hypoexcitable mPFCGlu neurons in LPS-treated WT mice, C3aR-null mPFCGlu neurons display hyperexcitability upon LPS treatment, and enhanced excitation of mPFCGlu neurons is anti-depressant, suggesting a protective role of C3aR deficiency in these circumstances. In conclusion, C3aR modulates susceptibility to LPS-induced depressive-like behaviors through mPFCGlu neuronal excitability. This study identifies C3aR as a pivotal intersection of complement activation, mPFC dysfunction, and depression and a promising therapeutic target for MDD.

Relationship between indices of insulin resistance and incident type 2 diabetes mellitus in Chinese adults.

BACKGROUND: Insulin resistance (IR) is a pivotal pathogenesis characteristic of type 2 diabetes mellitus (T2DM). The current study aimed to explore the association between triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-c), triglyceride-glucose (TyG), and triglyceride glucose-body mass index (TyG-BMI), and T2DM incidence. METHODS: A total of 116,855 Chinese adults aged over 20 without diabetes were included. Multivariate Cox regression analysis and restricted cubic spine were utilized to investigate the association between IR indicators and T2DM. The T2DM risk across different quartiles of IR parameters was compared using Kaplan-Meier curves. The receiver operating characteristic analysis was used to investigate the predictive potential of each IR indicator for future T2DM. RESULTS: A total of 2685 participants developed T2DM during a median follow-up of 2.98 years. The adjusted hazard ratios (HR) of incident T2DM were 1.177, 2.766, and 1.1018 for TG/HDL-c, TyG, and TyG-BMI, respectively. There were significant increasing trends of T2DM across the quartiles of TG/HDL-c, TyG, and TyG-BMI. The HRs of new-onset T2DM in the highest quartiles versus the lowest quartile of TG/HDL-c, TyG, and TyG-BMI were 3.298, 8.402, and 8.468. RCS revealed the nonlinear relationship between IR and T2DM risk. The correlations between IR and T2DM were more pronounced in subjects aged <40. TyG-BMI had the highest predictive value for incident T2DM (AUC = 0.774), with a cut-off value of 213.289. CONCLUSION: TG/HDL-c, TyG, and TyG-BMI index were all significantly positively associated with higher risk for future T2DM. Baseline TyG-BMI level had high predictive value for the identification of T2DM.

The association between long-term exposure to ambient PM2.5 and high-density lipoprotein cholesterol level among chinese middle-aged and older adults.

BACKGROUND: Recently, the impact of PM2.5 on human health has been intensively studied, especially the respiratory system. High-density lipoprotein plays a crucial role in removing excess cholesterol from cells and transporting it to the liver for excretion. However, the effects of ambient PM2.5 on high-density lipoprotein (HDL) level have not been further studied. Our research aims to investigate the potential association between ambient PM2.5 concentrations and high-density lipoprotein (HDL) levels within the middle-aged and older adults in China. METHODS: We employed data from individuals aged 45 years and above who were participants in Wave 3 of the China Health and Retirement Longitudinal Study (CHARLS). The high-quality, high-resolution PM2.5 exposure concentration data for each participant were obtained from the ChinaHighAirPollutants (CHAP) dataset, while the HDL levels were derived from blood samples collected during CHARLS Wave 3. This analysis constitutes a cross-sectional study involving a total of 12,519 participants. To investigate associations, we conducted multivariate linear regression analysis, supplemented by subgroup analysis. RESULTS: In this cross-sectional investigation, we discerned a negative association between prolonged exposure to ambient PM2.5 constituents and high-density lipoprotein (HDL) levels. The observed correlation between ambient PM2.5 and HDL levels suggests that older individuals residing in areas with elevated PM2.5 concentrations exhibit a reduction in HDL levels (Beta: -0.045; 95% CI: -0.056, -0.035; P < 0.001). Upon adjusting for age in Model I, the Beta coefficient remained consistent at -0.046 (95% CI: -0.056, -0.035; p < 0.001). This association persisted even after accounting for various potential confounding factors (Beta = -0.031, 95% CI: -0.041, -0.021, p < 0.001). CONCLUSIONS: Our study reveals a statistically significant negative correlation between sustained exposure to higher concentrations of ambient PM2.5 and high-density lipoprotein (HDL) levels among Chinese middle-aged and older individuals.

Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy.

Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc-. Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.

Development and Characterization of an Antioxidant and Antimicrobial Film Composited by Hydroxyethyl Cellulose and Sulfated Rice Bran Polysaccharides for Food Packaging.

The nonantimicrobial properties and relatively poor mechanical properties of hydroxyethyl cellulose (HEC) limit its use in packaging. Sulfated rice bran polysaccharides (SRBP) possess significant antioxidant and antimicrobial activities. The purpose of this study was to investigate the effect of different concentrations of SRBP on the physical and mechanical properties and the functional characteristics of HEC/SRBP films. The physical properties of the HEC/20% SRBP films, such as water resistance, water vapor barrier, light barrier, and tensile strength, improved significantly (p < 0.05) compared with those of the HEC films. Scanning electron microscopy and Fourier transform infrared spectrometry showed that HEC formed hydrogen bonds with SRBP and exhibited better compatibility. Thermogravimetric analysis revealed that the addition of SRBP was beneficial to the thermal stability of the films. In addition, the antioxidant and bacteriostatic properties of the films were enhanced by the addition of SRBP to HEC, with the 20% SRBP films showing the most significant enhancement in activity. Therefore, the HEC/20% SRBP films show potential for development for use as active food packaging.

Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) via regulating the synaptic plasticity in hippocampus.

TSPO, translocator protein (18 kDa) ligands have demonstrated consistent antidepression and anxiolytic effects in several preclinical studies. This study aimed to examine whether YL-IPA08[N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl) -7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, could alleviate anxiety-related behaviors induced by electric shock (ES) and investigate its underlying mechanism. As expected, we showed that chronic treatment with YL-IPA08 significantly reversed anxiety-related behaviors induced by electrical stimulation (0.5 mA, 12 times, duration 1s, interval 10s) exposure. Using the analysis of RNA-sequencing (RNA-seq) technology, it was found that the differential genes associated with the anxiolytic effect of YL-IPA08 were mainly related to synaptic plasticity. Furthermore, YL-IPA08 restored the decreased levels of brain-derived neurotrophic factor (BDNF), synapse-related protein (e.g. synapsin-1 and post-synaptic density95, PSD95), and the number of doublecortin (DCX) + neurons in the hippocampus of post-ES mice. In addition, YL-IPA08 also enhanced the dendritic complexity and dendritic spine density of hippocampal dentate gyrus (DG) granule neurons. Meanwhile, the induction of long-term potentiation (LTP) was significantly enhanced by YL-IPA08. In summary, the findings from the current study showed that YL-IPA08 exerted a clear anxiolytic effect, which might be partially mediated by promoting hippocampal neuroplasticity.

Analytical study of integrating downhole thermoelectric power generation with a coaxial borehole heat exchanger in geothermal wells.

Geothermal power generation employing Organic Rankine Cycle (ORC) technology is a widely acknowledged and conventional approach for harnessing geothermal energy. In an innovative advancement, we propose a novel design integrating downhole thermoelectric power generation with a coaxial borehole heat exchanger. This design aims to enhance the efficiency and sustainability of geothermal energy utilization. In this innovative design, the geothermal well is divided into two distinct sections: a power generation section and a heat exchanging section, achieved through the implementation of a packer positioned from the uppermost part of the targeted zone. The process involves the injection of cold fluid downhole via an insulated pipe. Subsequently, a portion of the injected fluid is directed to flow in reverse within the casing-tubing annulus above the packer, while another portion circulates into the casing-tubing annulus below the packer before ascending through the tubing. This dual flow mechanism establishes distinct cold and hot sources for the thermoelectric generator, a key feature facilitated by this innovative design. Analytical models detailing of downhole temperature distribution for thermoelectric power have been meticulously developed. A comprehensive case study, focusing on a geothermal well with 3000 m length of power generation section and 500 m heat exchanging section, has been conducted. The results indicate that a significant generating capacity could be achieved with a higher wellhead temperature, and the payback period under different carbon tax scenarios is about 6-8 year. Furthermore, the effects of injection rate, fluid diversion ratio, and casing-tubing configuration on power performance and thermal-electricity efficiency are also discussed. This method not only enables the concurrent harvesting of geothermal energy and power generation but also operates consistently throughout the year. The results thus emphasize the viability and economic feasibility of the proposed approach.

Nonlinear relationship between untraditional lipid parameters and the risk of prediabetes: a large retrospective study based on Chinese adults.

BACKGROUND: Abnormal lipid metabolism poses a risk for prediabetes. However, research on lipid parameters used to predict the risk of prediabetes is scarce, and the significance of traditional and untraditional lipid parameters remains unexplored in prediabetes. This study aimed to comprehensively evaluate the association between 12 lipid parameters and prediabetes and their diagnostic value. METHODS: This cross-sectional study included data from 100,309 Chinese adults with normal baseline blood glucose levels. New onset of prediabetes was the outcome of concern. Untraditional lipid parameters were derived from traditional lipid parameters. Multivariate logistic regression and smooth curve fitting were used to examine the nonlinear relationship between lipid parameters and prediabetes. A two-piecewise linear regression model was used to identify the critical points of lipid parameters influencing the risk of prediabetes. The areas under the receiver operating characteristic curve estimated the predictive value of the lipid parameters. RESULTS: A total of 12,352 participants (12.31%) were newly diagnosed with prediabetes. Following adjustments for confounding covariables, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol were negatively correlated with prediabetes risk. Conversely, total cholesterol, triglyceride (TG), lipoprotein combine index (LCI), atherogenic index of plasma (AIP), non-HDL-C, atherogenic coefficient, Castelli's index-I, remnant cholesterol (RC), and RC/HDL-C ratio displayed positive correlations. In younger adults, females, individuals with a family history of diabetes, and non-obese individuals, LCI, TG, and AIP exhibited higher predictive values for the onset of prediabetes compared to other lipid profiles. CONCLUSION: Nonlinear associations were observed between untraditional lipid parameters and the risk of prediabetes. The predictive value of untraditional lipid parameters for prediabetes surpassed that of traditional lipid parameters, with LCI emerging as the most effective predictor for prediabetes.

How to Apply Intraoperative Ultrasound when Spinal Trauma Surgery Is Performed in the Lateral Decubitus Position?

OBJECTIVE: At present, intraoperative ultrasound was widely used in spinal surgery. But there have been no reports on the use of intraoperative ultrasound in lateral decubitus position spinal surgery. The authors' research objective was to describe the applications of intraoperative ultrasound in spinal trauma surgery when performed in the lateral decubitus position. METHODS: Six patients with polytrauma who underwent surgery for spinal trauma between June 2020 and March 2022 and could not be operated on using a posterior approach in the prone position. All six patients underwent surgery in the lateral decubitus position. During surgery, a capsular bag had been designed and surgical field can be filled with normal saline for acoustic coupling, and then ultrasound was used to observe and guide decompression, and assess injuries of the neural elements such as the spinal cord. The data of preoperative and postoperative (12 months) American Spinal Injury Association impairment scale (AIS), follow-up time, operation time, blood loss, ultrasound signal change of spinal cord, ultrasound guide decompression, internal fixation (12 months), and fracture healing(12 months) were collected. RESULTS: The study included four males and two females whose ages ranged from 19 to 56 years old (41.5 ± 13.06 years old). Follow-up times ranged from 12 to 20 months (14.33 ± 2.75 months). The operation times ranged from 195 to 248 mins (222.16 ± 16.86 mins). The estimated volume of blood loss ranged from 280 to 450 mL (383.33 ± 55.58 mL). The six cases' AIS (preoperative vs. postoperative) were A versus A, C versus D, A versus B, B versus B, B versus C, and B versus C. Intraoperative ultrasound was performed successfully in all patients using our designed method. Intraoperative ultrasound observation revealed varying degrees of changes in spinal cord echo in all patients. Intraoperative ultrasound provided excellent assistance in spinal cord decompression during surgery. The surgery was completed successfully with no surgery-related complications till the last follow-up. At the time of last follow-up (median time of 12 months) satisfactory fracture reduction and good internal fixation was confirmed on postoperative computed tomography scans and radiographs. CONCLUSIONS: The authors represented the technology of intraoperative ultrasound in spinal trauma surgery when performed in the lateral decubitus position. This technology solves how to apply intraoperative ultrasound in lateral decubitus position.

Identification of hub genes based on integrated analysis of single-cell and microarray transcriptome in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating chronic cardiopulmonary disease without an effective therapeutic approach. The underlying molecular mechanism of PAH remains largely unexplored at single-cell resolution. METHODS: Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database (GSE210248) was included and analyzed comprehensively. Additionally, microarray transcriptome data including 15 lung tissue from PAH patients and 11 normal samples (GSE113439) was also obtained. Seurat R package was applied to process scRNA-seq data. Uniform manifold approximation and projection (UMAP) was utilized for dimensionality reduction and cluster identification, and the SingleR package was performed for cell annotation. FindAllMarkers analysis and ClusterProfiler package were applied to identify differentially expressed genes (DEGs) for each cluster in GSE210248 and GSE113439, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) were used for functional enrichment analysis of DEGs. Microenvironment Cell Populations counter (MCP counter) was applied to evaluate the immune cell infiltration. STRING was used to construct a protein-protein interaction (PPI) network of DEGs, followed by hub genes selection through Cytoscape software and Veen Diagram. RESULTS: Nineteen thousand five hundred seventy-six cells from 3 donors and 21,896 cells from 3 PAH patients remained for subsequent analysis after filtration. A total of 42 cell clusters were identified through UMAP and annotated by the SingleR package. 10 cell clusters with the top 10 cell amounts were selected for consequent analysis. Compared with the control group, the proportion of adipocytes and fibroblasts was significantly reduced, while CD8+ T cells and macrophages were notably increased in the PAH group. MCP counter revealed decreased distribution of CD8+ T cells, cytotoxic lymphocytes, and NK cells, as well as increased infiltration of monocytic lineage in PAH lung samples. Among 997 DEGs in GSE113439, module 1 with 68 critical genes was screened out through the MCODE plug-in in Cytoscape software. The top 20 DEGs in each cluster of GSE210248 were filtered out by the Cytohubba plug-in using the MCC method. Eventually, WDR43 and GNL2 were found significantly increased in PAH and identified as the hub genes after overlapping these DEGs from GSE210248 and GSE113439. CONCLUSION: WDR43 and GNL2 might provide novel insight into revealing the new molecular mechanisms and potential therapeutic targets for PAH.

Functional Characterization and Toxicological Study of Proanthocyanidins in Weaned Pigs.

Proanthocyanidin (PRO) has been implicated in a variety of biological functions, such as antibacterial, antioxidant, and anti-obesity effects. However, little is known about its safety dose for animals. To explore its safety and effect on growth performance and intestinal health, thirty weaned pigs were divided into five groups and fed with basal diet containing 0, 30, 300, 600, and 1200 mg/kg PRO for 42 days. Results showed that PRO supplementation at 30 and 300 mg/kg significantly decreased the feed/gain ratio (F:G) and diarrhea rate (p < 0.05). PRO also increased the digestibilities of dry matter, ether extract, gross energy, and ash (p < 0.05). Interestingly, PRO not only elevated the villus height and the ratio of villus height to crypt depth (V/C) in duodenum and jejunum (p < 0.01), but also decreased the crypt depth in the duodenum (p < 0.01). Moreover, PRO supplementation at 30, 300, and 600 mg/kg elevated the expression levels of mucin 1 (MUC1), MUC2, and fatty acid transport protein 1 (FATP-1) in the duodenum (p < 0.05). The expression levels of FATP-4 in jejunum and ileum were also elevated by PRO (p < 0.05). Importantly, histopathological findings of tissues (e.g., heart, liver, kidney, spleen, lungs, pancreas, thymus, mesenteric lymph nodes, stomach, small intestine), serum clinical chemistry, and major hematological parameters were not affected by PRO supplementation. These results suggest that PRO may act as a safe and effective supplement to decrease F:G and improve intestinal health in weaned pigs.

Upregulation of the key biomarker kinesin family member 20A (KIF20A) is associated with pulmonary artery hypertension.

OBJECTIVE: Pulmonary artery hypertension (PAH) is a complex, fatal disease with limited treatments. This study aimed to investigate possible key targets in PAH through bioinformatics. METHODS: GSE144274 were obtained from Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) between idiopathic pulmonary hypertension (IPAH) and healthy subjects were identified and analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed, and a protein-protein interaction (PPI) network was constructed using STRING. The hub genes were identified by MCODE method. The expression levels of hub genes were validated in vitro and in vivo models. Finally, the ROC analysis was performed based on the level of hub genes in clinical plasma samples. RESULTS: A total of 363 DEGs were identified. GO analysis on these DEGs were mainly enriched in cell division, inflammatory response, among others. In the KEGG pathways analysis, DEGs mainly involved in cytokine-cytokine receptor interaction, rheumatoid arthritis, and IL-17 signaling pathways were enriched. The DEGs were analyzed with the STRING for PPI network analysis, and 62 hub genes were identified by MCODE. Finally, 6 central genes, KIF18B, SPC25, DLGAP5, KIF20A, CEP55 and ANLN, were screened out due to their novelty role in PAH. The expression of KIF20A was validated to be significantly upregulated both in the lung tissue of hypoxia-induced pulmonary hypertension (HPH) mice and proliferative PASMCs. Additionally, KIF20A levels is evelated in PAH plasma and the area under the curve (AUC) to identify PAH was 0.8591 for KIF20A. CONCLUSION: The level of KIF20A elevates during the progression of PAH, which suggestes it could be a potential diagnostic and therapeutic target for the PAH.

Association Between Inflammatory Biomarkers and Contrast-induced Acute Kidney Injury in ACS Patients Undergoing Percutaneous Coronary Intervention: A Cross-sectional Study.

The present study aimed to evaluate the predictive role of inflammatory biomarkers in the development of contrast-induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The inflammatory biomarkers assessed were: platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), neutrophil-to-lymphocyte*platelet ratio (NLPR), systemic inflammatory index (SII), and systemic inflammation response index (SIRI). Overall, 950 patients undergoing PCI were enrolled. The frequency of CI-AKI was 15.2% (n = 144). The levels of NLR, MLR, NLPR, SII, and SIRI were higher in the CI-AKI group than in the Non-CI-AKI group (P < .05). The addition of NLR ≥2.96, dNLR ≥2.08, NLPR ≥.012, SII ≥558.04, and SIRI ≥1.13 to the Mehran score model significantly increased the area under the curve (P < .05). Multivariable logistic regression analyses indicated that inflammatory biomarkers were significantly associated with CI-AKI, including NLR ≥2.96 (OR = 1.588, P = .017), dNLR ≥2.08 (OR = 1.686, P = .007), SII ≥558.04 (OR = 1.521, P = .030), and SIRI ≥1.13 (OR = 1.601, P = .017). Therefore, inflammation is associated with the development of CI-AKI, and preoperative hematological inflammatory markers could predict the risk of CI-AKI in ACS patients undergoing PCI.

Cementless total hip arthroplasty for treatment of acetabular protrusion secondary to rheumatoid arthritis.

BACKGROUND: To explore the surgical technique and clinical outcomes of cementless total hip arthroplasty (THA) combined with impacted bone grafting for the treatment of moderate and severe acetabular protrusion with rheumatoid arthritis (RA). METHODS: From January 2010 to October 2020, 45 patients (56 hips), including 17 men (22 hips) and 28 women (34 hips) with acetabular impingement secondary to RA, were treated with bioprosthetic THA combined with autologous bone grafting at our hospital. According to the Sotello-Garza and Charnley classification criteria, there were 40 cases (49 hips) of type II (protrusio acetabuli 6-15 mm) and 5 cases (7 hips) of type III (protrusio acetabuli > 15 mm). At the postoperative follow-up, the ROM of the hip joint, the VAS score, and the Harris score were evaluated. The healing of the bone graft, the restoration of the hip rotation center, and the prosthesis loosening were assessed by plain anteroposterior radiographs. RESULTS: The average operation time was 95.53 ± 22.45 min, and the mean blood loss was 156.16 ± 69.25 mL. There were no neurovascular complications during the operation. The mean follow-up duration was 5.20 ± 1.20 years. The horizontal distance of the hip rotation center increased from preoperative 10.40 ± 2.50 mm to postoperative 24.03 ± 1.77 mm, and the vertical distance increased from preoperative 72.36 ± 3.10 mm to postoperative 92.48 ± 5.31 mm. The range of flexion motion of the hip joint increased from 39.48 ± 8.36° preoperatively to 103.07 ± 7.64° postoperatively, and the range of abduction motion increased from 10.86 ± 4.34° preoperatively to 36.75 ± 3.99° postoperatively. At the last follow-up, the Harris score increased from 37.84 ± 4.74 to 89.55 ± 4.05. All patients were able to move independently without assistance. CONCLUSIONS: Cementless THA combined with impacted grafting granule bone of the autogenous femoral head and biological acetabular cup can reconstruct the acetabulum, restore the rotation center of the hip joint, and achieve good medium-term outcomes in the treatment of moderate to severe acetabular herniation secondary to RA.

Predicting cerebral white matter lesions based on the platelet-to-white blood cell ratio in hypertensive patients.

Hypertension is a common chronic disease affecting many people. White matter lesions (WMLs) are one of the imaging features of cerebrovascular disease. Predicting the possibility of developing syncretic WMLs in patients with hypertension may contribute to the early identification of serious clinical conditions. This study aims to build a model to identify patients who suffered from moderate-to-severe WMLs by using recognized WMLs risk factors including age and history of diabetes and a new factor named platelet-to-white blood cell ratio (PWR). A total of 237 patients were included in this study. The Affiliated ZhongDa Hospital of Southeast University Research Ethics Committee approved this study (Ethics No. 2019ZDSYLL189-P01). We developed a nomogram to predict the risk of syncretic WMLs in patients with hypertension using the above factors. Higher total scores on the nomogram indicated a higher risk of syncretic WMLs. This means older age, smaller PWR, and patients suffering from diabetes contributed to a greater chance for the patient to suffer from syncretic WMLs. We used a decision analysis curve(DCA) to determine the net benefit of the prediction model. The DCA we constructed showed that using our model to decide whether patients suffered from syncretic WMLs or not was better than assuming they all suffered from syncretic WMLs or all WMLs-free. As a result, the area under the curve of our model was 0.787. By integrating PWR, history of diabetes, and age, we could estimate integrated WMLs in hypertensive patients. This study provides a potential tool to identify cerebrovascular disease in patients with hypertension.