Cost and related factors analysis for patients undergoing colon polyp surgery based on DRG mode.

OBJECTIVE: The aim of the study was to analyze the hospitalization costs of patients with intestinal polyps undergoing colonic polyp surgery and associated influencing factors and to explore the entry point of cost control and the way of fine management. PATIENTS AND METHODS: One year before (2021) and one year after (2022) the implementation of the Diagnosis Related Grouping (DRG), the patients receiving APC, CSP and EMR in GK39 (colonoscopy operation) group were included in a second Affiliated Hospital in Nanjing according to the Nanjing grouping scheme. Descriptive analysis method and multiple linear regression method were used for analysis. RESULTS: After the implementation of DRG in 2022, the average hospitalization cost of patients decreased by 19.46% compared with the same period last year. Before and after the implementation of DRG, medical technology costs accounted for the highest proportion of hospitalization costs. Age, hospitalization days, number of polyps, number of clamps and clinical pathway had statistically significant effects on hospitalization cost (p<0.05), among which hospitalization days, number of polyps, and number of clamps had the greatest impact on hospitalization cost, followed by age and clinical pathway. CONCLUSIONS: The implementation of DRG has a positive effect on guiding hospitalization cost control. It is suggested to realize accurate cost control by analyzing the cost structure of the disease group. Clinical pathway completion rate has a direct impact on the implementation effect of DRG, including cost control. It is suggested to refine clinical pathway management and achieve scientific cost control through continuous optimization and improvement of clinical pathway management.

p120 regulates E-cadherin expression in nasal epithelial cells in chronic rhinosinusitis.

BACKGROUND: The epithelial barrier plays an important role in the regulation of immune homeostasis. The effect of the immune environment on E-cadherin has been demonstrated in previous studies. This discovery prompted new research on the targeting mechanism of E-cadherin in chronic rhinosinusitis (CRS). METHODS: E-cadherin and p120 expression was determined by quantitative RT-PCR, and western blot. The interaction between E-cadherin and p120 was assessed by immunofluorescence staining and coimmunoprecipitation assays. Human nasal epithelial cells (HNECs) were cultured with submerged methods and transfected with p120-specific small interfering RNA. In other experiments, HNECs differentiated with the air-liquid interface (ALI) method were stimulated with various cytokines and Toll-like receptor (TLR) agonists. The barrier properties of differentiated HNECs were determined by assessing fluorescent dextran permeability. RESULTS: E-cadherin and p120 expression was decreased in HNECs from patients with CRS, and the p120 protein expression level was positively correlated with that of E-cadherin. Two isoforms of p120 (p120-1 and p120-3) were expressed in HNECs, with p120-3 being the main isoform. Knocking down p120 in HNECs cultured under submerged conditions significantly reduced the E-cadherin protein expression. The Rac1 inhibitor NSC23766 reversed the protein expression of E-cadherin in p120 knockdown experiments. Inflammatory mediators, including IL-4, TNF-α, TGF- ß, LPS and IFN-Î, reduced E-cadherin and p120 protein expression and increased paracellular permeability. Dexamethasone abolished the downregulation of E-cadherin and p120 caused by inflammatory mediators. CONCLUSIONS: p120 is involved in regulating E-cadherin protein expression in CRS. Dexamethasone may alleviate the reduction in E-cadherin and p120 protein expression caused by inflammatory mediators.

Long noncoding RNA PCAT-1 accelerates the metastasis of pancreatic cancer by repressing RBM5.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA PCAT-1 accelerates the metastasis of pancreatic cancer by repressing RBM5, by Y. Wang, X.-M. Jiang, Z.-X. Feng, X.-L. Li, W.-L. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (17): 7350-7355-DOI: 10.26355/eurrev_201909_18841-PMID: 31539121" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18841.

LINC01605 regulates proliferation, migration and invasion of colorectal cancer cells via targeting miR-3960/SOX11.

OBJECTIVE: We aimed to determine the expression level of long intergenic non-coding ribonucleic acid 1605 (LINC01605) in colorectal cancer (CRC), and to explore the effects of the LINC01605/microRNA (miR)-3960/sex-determining region Y-box 11 (SOX11) regulatory axis on the biological behaviors of CRC cells and the molecular mechanism therein. PATIENTS AND METHODS: Tissue specimens were collected from 38 patients with CRC, and the relative expression level of LINC01605 in the CRC tissues and CRC cells was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, the effects of LINC01605 on the proliferation, apoptosis, invasion and metastasis of CRC cells were observed via in vitro assays [cell counting kit (CCK)-8 assay, flow cytometry and transwell assay]. Besides, the possible miRNAs binding to LINC01605 were predicted by the bioinformatics method, and they were screened and verified using qRT-PCR and Dual-Luciferase reporter gene assay. Finally, the downstream target genes of miR-3960 were predicted by means of bioinformatics, and they were also screened and confirmed via qRT-PCR and Dual-Luciferase reporter gene assay. RESULTS: According to the results of qRT-PCR, the expression of LINC01605 was up-regulated in 31 out of 38 cases of CRC tissue specimens, and its expression in CRC cells was higher than that in normal colorectal cells. The results of in vitro assays revealed that the proliferation, migration and invasion abilities of CRC cells were weakened, with an increased apoptosis rate after interference with LINC01605 expression. Based on the results of qRT-PCR and Dual-Luciferase reporter gene assay, miR-3960 was the target of LINC01605, while SOX11 was the target of miR-3960. Moreover, the expression of miR-3960 rose, but that of SOX11 declined after interference with LINC01605 expression. It was found through Western blotting that the protein expression of SOX11 was lowered after interference with LINC01605 expression. CONCLUSIONS: LINC01605 has an up-regulated expression in CRC, and accelerates the proliferation, migration and metastasis of CRC cells by the miR-3960/SOX11 regulatory axis.

Genome-wide association studies for growth-related traits in a crossbreed pig population.

Growth-related traits are important economic traits in the pig industry that directly influence pork production efficiency. To detect quantitative trait loci and candidate genes affecting growth traits, genome-wide association studies were performed for backfat thickness (BF) and loin muscle depth (LMD) in 370 Chuying-black pigs using Illumina PorcineSNP50 BeadChip array. We totally identified 14 BF-associated SNPs, which included 11 genome-wide SNPs (P < 1.39E-06) and 3 chromosome-wide suggestive SNPs (P < 2.79E-05) and for LMD, 9 SNPs surpassed the genome-wide significant threshold (P < 1.39E-06). These SNPs explained 30.33 and 27.51% phenotypic variance for BF and LMD respectively. Furthermore, 14 and 9 genes nearest to the significant SNPs were selected to be candidate genes, including MAGED1, GPHN, CCSER1, and GUCY2D for BF and PARM1, COL18A1, HSF5, and SCML2 genes for LMD. One significant SNP, which explained 6.07% of phenotypic variance for BF, mapped to a pleiotropic quantitative trait locus with a 494-kb interval. Together, the SNPs and candidate genes identified in this study will advance our understanding of the complex genetic architecture of BF and LMD traits, and they will also provide important clues for future implementation of a genomic selection program in Chuying-black pigs.

Long non-coding RNA NR2F1-AS1 promoted neuroblastoma progression through miR-493-5p/TRIM2 axis.

OBJECTIVE: Long noncoding RNA (lncRNA) plays a vital role in the progression of various cancers. However, the potential mechanisms of NR2F1-AS1 in the tumorigenesis of neuroblastoma (NB) have not been determined. PATIENTS AND METHODS: The expression levels of NR2F1-AS1, miR-493 and TRIM2 were detected by RT-qPCR. The downstream target genes of NR2F1-AS1 or miR-493 were predicted by bioinformatics analysis (http://starbase.sysu.edu.cn/), which was further indicated by Luciferase reporter and RNA immunoprecipitation (RIP) assays. CCK-8, transwell, and TUNEL assays were performed to determine the viability, migration, invasion and apoptosis of NB cells. RESULTS: NR2F1-AS1 was highly expressed and miR-493 was lowly expressed in NB tissues and cell lines. The high expression of NR2F1-AS1 was associated with poor prognosis in NB. NR2F1-AS1 knockdown inhibited proliferation, migration, and invasion, and accelerated apoptosis of NB cells. MiR-493 was a downstream target of NR2F1-AS1, and the silencing of miR-493 reversed NR2F1-AS1 knockdown-attenuated progression of NB. Moreover, TRIM2 was demonstrated to be directly targeted by miR-493, and the upregulation of TRIM2 could abolish the inhibitory effect of miR-493 overexpression on the progression of NB. Finally, it was found that NR2F1-AS1 regulated TRIM2 expression by sponging miR-493. CONCLUSIONS: The present study demonstrated that NR2F1-AS1 promoted the progression of NB through the miR-493/TRIM2 axis. This finding may provide new insight into the treatment of NB.

Diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma.

OBJECTIVE: This study aims to clarify potential diagnostic and prognostic values of KLK11 in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: KLK11 levels in 81 primary NPC tissues, 24 recurrent NPC tissues, and 60 nasopharyngeal tissues with chronic mucosal inflammation were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, receiver operating characteristic (ROC) curves were depicted for assessing the diagnostic value of KLK11 in primary and recurrent NPC. Next, correlation between KLK11 level and pathological indexes of NPC patients was analyzed by Chi-square test. Enrolled NPC patients were followed up for 5 years, and the follow-up data were recorded to determine the potential influence of KLK11 on overall survival by Kaplan-Meier method. In addition, Cox regression model was applied for assessing factors that could affect prognosis of NPC patients. RESULTS: It was found that KLK11 level was higher in primary NPC tissues than that in nasopharyngeal tissues with chronic mucosal inflammation. In recurrent NPC tissues, KLK11 was upregulated relative to primary ones. In addition, ROC curves revealed a certain diagnostic value of KLK11 in NPC. Overall survival was worse in primary and recurrent NPC patients expressing a high level of KLK11. By analyzing the pathological indexes of NPC patients, KLK11 level was found to be correlated with age, T stage, and clinical stage of NPC patients. Furthermore, KLK11 level was found to be the risk factor influencing the survival of NPC patients. CONCLUSIONS: KLK11 is upregulated in NPC tissues, and unfavorable to the prognosis of NPC. Besides, it can be utilized as a potential hallmark for diagnosing NPC.

STYK1 promotes the malignant progression of laryngeal squamous cell carcinoma through targeting TGF-ß1.

OBJECTIVE: The aim of this study was to uncover the expression characteristic and biological function of STYK1 in the progression of laryngeal squamous cell carcinoma (LSCC), and to explore the underlying mechanism. PATIENTS AND METHODS: Expression level of STYK1 in 44 paired LSCC and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between STYK1 level and clinical parameters of LSCC patients was analyzed. Subsequently, the regulatory effect of STYK1 on the proliferative ability of AMC-HN-8 and Hep-2 cells was evaluated by cell counting kit-8 (CCK-8) assay and colony formation assay. Dual-Luciferase reporter gene assay and rescue experiments were conducted to uncover the role of STYK1/TGF-ß1 axis in regulating the progression of LSCC. RESULTS: STYK1 was significantly up-regulated in LSCC tissues than that of adjacent normal tissues (p<0.05). LSCC patients with high expression level of STYK1 exhibited significantly higher clinical stage and lower survival rate (p<0.05). Knockdown of STYK1 remarkably attenuated viability and clonality in Hep-2 cells, while overexpression of STYK1 achieved the opposite trends in AMC-HN-8 cells (p<0.05). TGF-ß1 was confirmed to be the direct target binding STYK1, whose expression level was negatively regulated by STYK1. TGF-ß1 was significantly down-regulated in LSCC tissues  (p<0.05). Meanwhile, its low expression predicted significantly poor prognosis of LSCC patients. In addition, TGF-ß1 was responsible for STYK1-regulated malignant progression of LSCC. CONCLUSIONS: STYK1 is upregulated in LSCC and is closely associated with T stage and poor prognosis. Furthermore, STYK1 promotes the proliferative ability of LSCC cells through targeting TGF-ß1, thus aggravating the malignant progression of LSCC.

LncRNA NEAT1 regulates proliferation, apoptosis and invasion of liver cancer.

OBJECTIVE: The occurrence and progression of hepatocellular carcinoma (HCC) is a multi-step complex process and the exact molecular mechanisms remain to be elucidated. LncRNA NEAT1 is involved in tumorigenesis and progression. However, the role of LncRNA NEAT1 in HCC remains unclear. PATIENTS AND METHODS: The tumor tissues and adjacent tissues of HCC patients were collected and LncRNA NEAT1 expression was detected by Real time PCR. The hepatoma cell line HepG2 was cultured and transfected with lnc RNA NEAT1 siRNA or lnc RNA NEAT1 plasmid followed by analysis of LncRNA NEAT1 expression, cell proliferation by MTT assay, as well as Caspase 3 activity. In addition, cell apoptosis and cell cycle were assessed by flow cytometry and cell invasion was measured by transwell chambers. The expression of EGFR, Bax and Bcl-2 was detected by Western blot. RESULTS: LncRNA NEAT1 expression was significantly increased in HCC tissues compared with adjacent tissues (p < 0.05). Compared with the siRNA group, transfection of lncRNA NEAT1 siRNA into HepG2 cells significantly inhibited cell proliferation, increased Caspase 3 activity and apoptosis, reduced cell invasion, as well as arrested cell cycle (p < 0.05). Meanwhile, lncRNA NEAT1 siRNA also significantly decreased Bcl-2 and EGFR expression and increased Bax expression (p < 0.05). Transfection of lncRNA NEAT1 plasmid in hepatoma cells HepG2 reversed the above changes, compared with vector group, the differences were statistically significant (p < 0.05). CONCLUSIONS: LncRNA NEAT1 expression is increased in liver cancer tissues. Down-regulation of LncRNA NEAT1 can inhibit EGFR expression and promote hepatoma cell apoptosis, inhibit cell cycle, thus inhibiting tumor proliferation and invasion.

Long noncoding RNA PCAT-1 accelerates the metastasis of pancreatic cancer by repressing RBM5.

OBJECTIVE: The role of long noncoding RNAs (lncRNAs) is vital in tumor progression. Our study aims to identify the role of PCAT-1 in the metastasis of pancreatic cancer. PATIENTS AND METHODS: Real time-quantitative polymerase chain reaction (RT-qPCR) was used to measure PCAT-1 expression in 50 pancreatic cancer patients' tissues. Furthermore, to identify the function of PCAT-1 in pancreatic cancer in vitro wound healing assay and transwell assay were conducted. Besides, RT-qPCR and Western blot assay were performed to explore the underlying mechanism. RESULTS: The expression level of PCAT-1 was significantly upregulated in pancreatic cancer samples compared with adjacent tissues. Moreover, cell migration and cell invasion were inhibited via knockdown of PCAT-1 in pancreatic cancer cells. Moreover, the mRNA and protein expression of RBM5 was upregulated via knockdown of PCAT-1 in pancreatic cancer cells. Furthermore, the RBM5 expression level was negatively related to the PCAT-1 expression level in pancreatic cancer tissues. CONCLUSIONS: This study suggests that PCAT-1 acts as an oncogene in pancreatic cancer and promotes cell metastasis via inhibiting RBM5, which might be a novel therapeutic strategy in pancreatic cancer.

Correction: Exosomal Wnt-induced dedifferentiation of colorectal cancer cells contributes to chemotherapy resistance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

MicroRNA-328 acts as an anti-oncogene by targeting ABCG2 in gastric carcinoma.

OBJECTIVE: To explore the regulatory mechanism of microRNA-328 expression level by targeting the protein ATP Binding Cassette Transporter G2 (ABCG2) in gastric cancer cells and seek for a biological marker of predicting gastric cancer. PATIENTS AND METHODS: SGC-7901 and MKN-28 human gastric cancer cell lines were cultured. Meanwhile, paired gastric cancer pathological tissues and the corresponding adjacent normal tissues were collected. Western blot analysis was used to validate the protein expression of ABCG2. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis was used to detect the mRNA expression level of miR-328 and ABCG2. Cell counting kit-8 (CCK-8) and colony formation assay were performed to validate the proliferous ability of human gastric cancer cells. The transwell invasion and migration were operated to determine the migratory and invasive capacity. Dual-Luciferase reporter assay, qRT-PCR and Western blot were used to prove the target of miR-328. RESULTS: Bioinformatics analysis made a prediction that ABCG2 was a direct functional target of miR-328. Position 619-625 of ABCG2 3'-UTR had a space structure that was complementary to miR-328 by bioinformatics analysis, and there was a significant reduction in the level of miR-328 in human gastric cancer cell lines and tissues. The expression of miR-328 down-regulated proliferation, invasion and migration of human gastric cancer cells in vitro, while silencing of miR-328 accelerated proliferation, invasion and migration of human gastric cancer cells in vitro. All results displayed ABCG2 was direct target protein of miR-328 owing the binding site and they presented a negative correlation. CONCLUSIONS: ABCG2 is the target protein of miR-328. It presents a negative correlation of the expression level between miR-328 and ABCG2. Down-regulation of miR-328 inhibits the proliferation, invasion and migration of gastric cancer cell lines. MiR-328 could predict generation and development of gastric cancer as a biomarker.

Correlations of serum homocysteine, VEGF and gastrin 17 with gastric cancer and precancerous lesions.

OBJECTIVE: To investigate the correlations of Homocysteine (Hcy), vascular endothelial growth factor (VEGF), and serum gastrin 17 (G17) with gastric cancer and precancerous lesions. PATIENTS AND METHODS: A total of 56 patients with gastric cancer (gastric cancer group) and 53 patients with precancerous lesions (precancerous lesion group) admitted to Heze Municipal Hospital from January 2017 to October 2018 were selected, and 50 healthy subjects undergoing the physical examination in the same period were selected as control group. The levels of serum Hcy, VEGF, and G17 in the three groups were compared, and the relations of each index with clinicopathological characteristics of gastric cancer were analyzed. RESULTS: The levels of serum Hcy, VEGF-A, VEGF-C, VEGF-D, and G17 in gastric cancer group and precancerous lesion group were higher than in control group, and those in gastric cancer group were higher than in precancerous lesion group (p<0.05). Besides, the high expression levels of serum Hcy, VEGF, and G17 had evident correlations with the tumor-node-metastasis (TNM) stage, Lauren type, infiltration depth, and lymph node metastasis of gastric cancer (p<0.05). CONCLUSIONS: Hcy, VEGF, and G17 can exhibit different levels of expressions in precancerous lesions. They are also highly expressed in gastric cancer. Besides, they are involved in the occurrence and development of gastric cancer and can be regarded as crucial indexes with clinical significance for the differential diagnosis of gastric cancer and precancerous lesions in the early stage.

Effects of Integrin ß1 on behavior and neurovascular regeneration in rats with cerebral ischemia-reperfusion injury.

OBJECTIVE: The aim of this study is to investigate the effect of Integrin ß1 on neurological behavior and neurovascular regeneration in rats with a cerebral ischemia-reperfusion injury. MATERIALS AND METHODS: Rat middle cerebral artery occlusion (MCAO) was performed with a modified suture embolization method. Neurological function score of each rat was recorded. Cerebral infarct volume was calculated by Image J after TTC stain. Subsequently, behavioral tests were performed to evaluate neuronal damage, including griping strength test, corner test, cylinder test and sucrose preference test. The expression levels of VEGF, HIF-1α, Claudin5, and ZO-1 in rat brain tissues were detected by Western blot and quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR), respectively. RESULTS: Neurological function score of the rat was remarkably decreased after cerebral ischemia-reperfusion. Anti-Integrin ß1 administration aggravated neurological deficit and increased cerebral infarct volume of I/R rats. Symptoms of hemidysesthesia, dyskinesia, and affective disorder of rats were worse after anti-Integrin ß1 administration in I/R rats. Anti-Integrin ß1 administration downregulated VEGF and HIF-1α in rat brain tissues (p<0.05). However, no significant differences in Claudin5 and ZO-1 expressions were found before and after Integrin ß1 treatment. CONCLUSIONS: The inhibition of Integrin ß1 pathway during cerebral ischemia-reperfusion aggravates the behavior and neurovascular regeneration of I/R rats. In the process of cerebral ischemia-reperfusion, Integrin ß1 plays a key role in the repair and protection of neurovascular units by promoting angiogenesis.

Exosomal Wnt-induced dedifferentiation of colorectal cancer cells contributes to chemotherapy resistance.

Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.

Transplantation of Human umbilical cord mesenchymal stem cells promotes functional recovery after spinal cord injury by blocking the expression of IL-7.

OBJECTIVE: This research aimed to investigate the therapeutic effects of transplanted human umbilical cord mesenchymal stem cells (hUCMSCs) on spinal cord injury in mice and to explore its molecular mechanism. MATERIALS AND METHODS: Spinal cord injury model in C57BL/6J mice was established. On the 10th day of SCI, hUCMSCs were injected into the center of spinal cord injury area (hUCMSC), and control groups (Control) were injected with an equal amount of medium. Western blotting, Real Time-PCR, immunohistochemistry, and flow cytometry, were used to analyze the content of IL-7, inflammatory cytokines, and macrophages after spinal cord injury in different groups. Open field and Rota-Rod tests were used to determine the effect of hUCMSC transplantation on motor function recovery in SCI mice. RESULTS: Compared with the control mice, hUCMSC transplantation therapy significantly improved the motor function, myelin, and nerve cell survival in spinal cord injury site in SCI mice. It also reduced the expression of IL-7, IFN-γ, and TNF-α in injured sites but increased IL-4 and IL-13 expression and promoted the activation of M2 macrophages at the site of injury. CONCLUSIONS: Transplantation of hUCMSCs in SCI mice can promote the polarization of M2 macrophages by reducing the expression of IL-7 in the injured site, thereby weakening the inflammatory response at the injured site, promoting the repair of the injured site and improving the motor function.

A volumetric intracoronary ultrasonographic study of coronary bifurcation lesions.

OBJECTIVE: To evaluate the plaque distribution and composition pattern in the left main coronary artery (LMCA) disease using intracoronary ultrasound. PATIENTS AND METHODS: Intravascular ultrasound data of 50 patients from the January 2010 to December 2015 with significant LMCA bifurcation lesions, with angiographic diameter stenosis >50%, and requiring revascularization, were evaluated. Plaque burden and percentage of necrotic core (% NC) at the minimal lumen area site and maximal % NC site were measured in different segments. The segments that were included in the study are as follows: segment 1: proximal LMCA, segment 2: left anterior descending (LAD) ostium, segment 3: left circumflex branch (LCX) ostium, segment 4: proximal LAD, segment 5: proximal LCX. According to its relationship with the bifurcation ridge, the blood vessel wall was divided into the contralateral bifurcation ridge blood vessel wall and bifurcation ridge blood vessel wall. RESULTS: Plaque burden results showed that the plaque eccentricity index of segment 2 and segment 3 was significantly higher than that of the other segments at sites of the minimal lumen area and maximal % NC with a statistically significant difference (p<0.05). Plaque eccentricity index of contralateral bifurcation ridge was significantly higher than that of the bifurcation ridge, and the difference was statistically significant (p<0.05). Analysis of plaque composition showed the fibrous tissue percentage of segment 2 and segment 3 was significantly higher than the other segments that at the sites of minimal lumen area and the maximal % NC site. The fibrous percentage of the contralateral bifurcation ridge was significantly lower than that of the bifurcation ridge. CONCLUSIONS: Intravascular ultrasound is an effective way for detecting the distribution and composition of the atherosclerotic plaque at the left main coronary artery bifurcation and is of great significance to adjuvant interventional therapy.

TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells.

OBJECTIVE: Hypoxia has been shown to inhibit reactive oxygen species (ROS) production in nucleus pulposus (NP) cells. The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been reported to suppress oxidative stress. We sought to explore the role of TIGAR in the effect of hypoxia on ROS production and apoptosis. METHODS: An intervertebral disc degeneration (IDD) model of Sprague-Dawley (SD) rat caudal spine was established by puncturing the Co6-7 disc. TIGAR expression was detected by immunohistochemistry and western blotting in human and SD rat NP tissues of degenerated discs. Rat primary NP cells treated with hypoxia and cobalt chloride (CoCl2) were analyzed by western blotting for TIGAR expression. After TIGAR silence with TIGAR siRNA transfection, apoptosis percentage, mitochondrial and total intracellular ROS levels were measured. H2O2 was used to further check the effects of TIGAR on oxidative stress. Finally, NADPH/NADP+ and GSH/GSSH ratio were examined after TIGAR silencing under hypoxic conditions and after H2O2 treatment. RESULTS: A degree-dependent increase in TIGAR expression was observed in human and rat degenerated NP tissues. Hypoxia and hypoxia-inducer CoCl2 enhanced TIGAR and P53 expressions in rat NP cells. TIGAR silence reversed the inhibitory effects of hypoxia on intracellular and mitochondrial ROS production, as well as apoptosis percentage. However, TIGAR silence aggravated H2O2-induced ROS production. In addition, TIGAR increased NADPH/NADP+ and GSH/GSSH ratio in NP cells. CONCLUSIONS: These results suggested that TIGAR appears to mediate the protective role of hypoxia on ROS production and apoptosis percentage by enhancing NADPH/NADP+ and GSH/GSSH ratio.

Tau-mediated iron export prevents ferroptotic damage after ischemic stroke.

Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.