Search

Zn2+ is an important contributor to ischemic brain injury and recent studies support the hypothesis that mitochondria are key sites of its injurious effects. In murine hippocampal slices (both sexes) subjected to oxygen glucose deprivation (OGD), we found that Zn2+ accumulation and its entry into mitochondria precedes and contributes to the induction of acute neuronal death. In addition, if the ischemic episode is short (and sublethal), there is ongoing Zn2+ accumulation in CA1 mitochondria after OGD that may contribute to their delayed dysfunction. Using this slice model of sublethal OGD, we have now examined Zn2+ contributions to the progression of changes evoked by OGD and occurring over 4-5 hours. We detected progressive mitochondrial depolarization occurring from ∼ 2 hours after ischemia, a large increase in spontaneous synaptic activity between 2-3 hours, and mitochondrial swelling and fragmentation at 4 hours. Blockade of the primary route for Zn2+ entry, the mitochondrial Ca2+ uniporter (MCU; with ruthenium red, RR) or Zn2+ chelation shortly after OGD withdrawal substantially attenuated the mitochondrial depolarization and the changes in synaptic activity. RR also largely reversed the mitochondrial swelling. Finally, using an in vivo rat (male) asphyxial cardiac arrest (CA) model of transient global ischemia, we found that ∼8 min asphyxia induces considerable injury of CA1 neurons 4 hours later that is associated with strong Zn2+ accumulation within many damaged mitochondria. These effects were substantially attenuated by infusion of RR upon reperfusion. Our findings highlight mitochondrial Zn2+ accumulation after ischemia as a possible target for neuroprotective therapy.SIGNIFICANCE STATEMENT:Brain ischemia is a leading cause of mortality and long-term disability that still lacks effective treatment. After transient ischemia delayed death of neurons occurs in vulnerable brain regions. There is a critical need to understand mechanisms of this delayed neurodegeneration which can be targeted for neuroprotection. We found progressive and long-lasting mitochondrial Zn2+ accumulation to occur in highly vulnerable CA1 neurons after ischemia. Here we demonstrate that this Zn2+ accumulation contributes strongly to deleterious events occurring after ischemia including mitochondrial dysfunction, swelling and structural changes. We suggest that this mitochondrial Zn2+ entry may constitute a promising target for development of therapeutic interventions to be delivered after termination of an episode of transient global ischemia.

Excitotoxic Ca2+ accumulation contributes to ischemic neurodegeneration, and Ca2+ can enter the mitochondria through the mitochondrial calcium uniporter (MCU) to promote mitochondrial dysfunction. Yet, Ca2+-targeted therapies have met limited success. A growing body of evidence has highlighted the underappreciated importance of Zn2+, which also accumulates in neurons after ischemia and can induce mitochondrial dysfunction and cell death. While studies have indicated that Zn2+ can also enter the mitochondria through the MCU, the specificity of the pore's role in Zn2+-triggered injury is still debated. Present studies use recently available MCU knockout mice to examine how the deletion of this channel impacts deleterious effects of cytosolic Zn2+ loading. In cultured cortical neurons from MCU knockout mice, we find significantly reduced mitochondrial Zn2+ accumulation. Correspondingly, these neurons were protected from both acute and delayed Zn2+-triggered mitochondrial dysfunction, including mitochondrial reactive oxygen species generation, depolarization, swelling and inhibition of respiration. Furthermore, when toxic extramitochondrial effects of Ca2+ entry were moderated, both cultured neurons (exposed to Zn2+) and CA1 neurons of hippocampal slices (subjected to prolonged oxygen glucose deprivation to model ischemia) from MCU knockout mice displayed decreased neurodegeneration. Finally, to examine the therapeutic applicability of these findings, we added an MCU blocker after toxic Zn2+ exposure in wildtype neurons (to induce post-insult MCU blockade). This significantly attenuated the delayed evolution of both mitochondrial dysfunction and neurotoxicity. These data-combining both genetic and pharmacologic tools-support the hypothesis that Zn2+ entry through the MCU is a critical contributor to ischemic neurodegeneration that could be targeted for neuroprotection.

Mitochondrial Zn2+ accumulation, particularly in CA1 neurons, occurs after ischemia and likely contributes to mitochondrial dysfunction and subsequent neurodegeneration. However, the relationship between mitochondrial Zn2+ accumulation and their disruption has not been examined at the ultrastructural level in vivo. We employed a cardiac arrest model of transient global ischemia (TGI), combined with Timm's sulfide silver labeling, which inserts electron dense metallic silver granules at sites of labile Zn2+ accumulation, and used transmission electron microscopy (TEM) to examine subcellular loci of the Zn2+ accumulation. In line with prior studies, TGI-induced damage to CA1 was far greater than to CA3 pyramidal neurons, and was substantially progressive in the hours after reperfusion (being significantly greater after 4- than 1-hour recovery). Intriguingly, TEM examination of Timm's-stained sections revealed substantial Zn2+ accumulation in many postischemic CA1 mitochondria, which was strongly correlated with their swelling and disruption. Furthermore, paralleling the evolution of neuronal injury, both the number of mitochondria containing Zn2+ and the degree of their disruption were far greater at 4- than 1-hour recovery. These data provide the first direct characterization of Zn2+ accumulation in CA1 mitochondria after in vivo TGI, and support the idea that targeting these events could yield therapeutic benefits.

Ischemic stroke is a major cause of death and disabilities worldwide, and it has been long hoped that improved understanding of relevant injury mechanisms would yield targeted neuroprotective therapies. While Ca2+ overload during ischemia-induced glutamate excitotoxicity has been identified as a major contributor, failures of glutamate targeted therapies to achieve desired clinical efficacy have dampened early hopes for the development of new treatments. However, additional studies examining possible contributions of Zn2+, a highly prevalent cation in the brain, have provided new insights that may help to rekindle the enthusiasm. In this review, we discuss both old and new findings yielding clues as to sources of the Zn2+ that accumulates in many forebrain neurons after ischemia, and mechanisms through which it mediates injury. Specifically, we highlight the growing evidence of important Zn2+ effects on mitochondria in promoting neuronal injury. A key focus has been to examine Zn2+ contributions to the degeneration of highly susceptible hippocampal pyramidal neurons. Recent studies provide evidence of differences in sources of Zn2+ and its interactions with mitochondria in CA1 versus CA3 neurons that may pertain to their differential vulnerabilities in disease. We propose that Zn2+-induced mitochondrial dysfunction is a critical and potentially targetable early event in the ischemic neuronal injury cascade, providing opportunities for the development of novel neuroprotective strategies to be delivered after transient ischemia.

Excitotoxic Zn2+ and Ca2+ accumulation contributes to neuronal injury after ischemia or prolonged seizures. Synaptically released Zn2+ can enter postsynaptic neurons via routes including voltage sensitive Ca2+ channels (VSCC), and, more rapidly, through Ca2+ permeable AMPA channels. There are also intracellular Zn2+ binding proteins which can either buffer neuronal Zn2+ influx or release bound Zn2+ into the cytosol during pathologic conditions. Studies in culture highlight mitochondria as possible targets of Zn2+; cytosolic Zn2+ can enter mitochondria and induce effects including loss of mitochondrial membrane potential (ΔΨm), mitochondrial swelling, and reactive oxygen species (ROS) generation. While brief (5 min) neuronal depolarization (to activate VSCC) in the presence of 300 μM Zn2+ causes substantial delayed neurodegeneration, it only mildly impacts acute mitochondrial function, raising questions as to contributions of Zn2+-induced mitochondrial dysfunction to neuronal injury. Using brief high (90 mM) K+/Zn2+ exposures to mimic neuronal depolarization and extracellular Zn2+ accumulation as may accompany ischemia in vivo, we examined effects of disrupted cytosolic Zn2+ buffering and/or the presence of Ca2+, and made several observations: 1. Mild disruption of cytosolic Zn2+ buffering-while having little effects alone-markedly enhanced mitochondrial Zn2+ accumulation and dysfunction (including loss of ∆Ψm, ROS generation, swelling and respiratory inhibition) caused by relatively low (10-50 μM) Zn2+ with high K+. 2. The presence of Ca2+ during the Zn2+ exposure decreased cytosolic and mitochondrial Zn2+ accumulation, but markedly exacerbated the consequent dysfunction. 3. Paralleling effects on mitochondria, disruption of buffering and presence of Ca2+ enhanced Zn2+-induced neurodegeneration. 4. Zn2+ chelation after the high K+/Zn2+ exposure attenuated both ROS production and neurodegeneration, supporting the potential utility of delayed interventions. Taken together, these data lend credence to the idea that in pathologic states that impair cytosolic Zn2+ buffering, slow uptake of Zn2+ along with Ca2+ into neurons via VSCC can disrupt the mitochondria and induce neurodegeneration.

Excitotoxic mechanisms contribute to the degeneration of hippocampal pyramidal neurons after recurrent seizures and brain ischemia. However, susceptibility differs, with CA1 neurons degenerating preferentially after global ischemia and CA3 neurons after limbic seizures. Whereas most studies address contributions of excitotoxic Ca2+ entry, it is apparent that Zn2+ also contributes, reflecting accumulation in neurons either after synaptic release and entry through postsynaptic channels or upon mobilization from intracellular Zn2+-binding proteins such as metallothionein-III (MT-III). Using mouse hippocampal slices to study acute oxygen glucose deprivation (OGD)-triggered neurodegeneration, we found evidence for early contributions of excitotoxic Ca2+ and Zn2+ accumulation in both CA1 and CA3, as indicated by the ability of Zn2+ chelators or Ca2+ entry blockers to delay pyramidal neuronal death in both regions. However, using knock-out animals (of MT-III and vesicular Zn2+ transporter, ZnT3) and channel blockers revealed substantial differences in relevant Zn2+ sources, with critical contributions of presynaptic release and its permeation through Ca2+- (and Zn2+)-permeable AMPA channels in CA3 and Zn2+ mobilization from MT-III predominating in CA1. To assess the consequences of the intracellular Zn2+ accumulation, we used OGD exposures slightly shorter than those causing acute neuronal death; under these conditions, cytosolic Zn2+ rises persisted for 10-30 min after OGD, followed by recovery over ∼40-60 min. Furthermore, the recovery appeared to be accompanied by mitochondrial Zn2+ accumulation (via the mitochondrial Ca2+ uniporter MCU) in CA1 but not in CA3 neurons and was markedly diminished in MT-III knock-outs, suggesting that it depended upon Zn2+ mobilization from this protein.Significance statementThe basis for the differential vulnerabilities of CA1 versus CA3 pyramidal neurons is unclear. The present study of events during and after acute oxygen glucose deprivation highlights a possible important difference, with rapid synaptic entry of Ca2+ and Zn2+ contributing more in CA3, but with delayed and long-lasting accumulation of Zn2+ within mitochondria occurring in CA1 but not CA3 pyramidal neurons. These data may be consistent with observations of prominent mitochondrial dysfunction as a critical early event in the delayed degeneration of CA1 neurons after ischemia and support a hypothesis that mitochondrial Zn2+ accumulation in the early reperfusion period may be a critical and targetable upstream event in the injury cascade.

The interface characteristics, bending and impact behavior, as well as fracture characteristics of stainless steel clad plates fabricated by vacuum hot rolling at different rolling temperatures of 1100°C, 1200°C and 1300°C are investigated in detail. The interface bonding strength is gradually increased with the increasing rolling temperature due to the sufficient diffusion behavior of alloy element. The bending toughness and impact toughness are gradually decreased, while the bending strength increase with the increase of the rolling temperature, which is attributed to mechanisms of matrix softening and interface strengthening at high rolling temperature. Due to the weak interface at 1100°C, the bending and impact crack propagation path was displaced by delamination cracks, which in turn lead to reduction in stress intensity of the main crack, playing an effective role in toughening the stainless steel clad plates. Moreover, the impact fracture morphologies of clad plates show a typical ductile-brittle transition phenomenon, which is attributed to the matrix softening behavior with the increasing rolling temperature. [ABSTRACT FROM AUTHOR]

This paper investigated the microstructure and mechanical properties of Q235/304 stainless steel clad plate welding seam produced by hybrid welding of tungsten inert gas welding (TIG) and metal active gas arc welding (MAG). The results showed that the dual phases containing ferrite and austenite appeared in the stainless steel covering welding (SSCW), while the partial martensite phases appeared in the carbon steel backing welding (CSBW), which is attributed to the dilution behavior of Ni and Cr elements from stainless steel to the Q235 steel results into the movement of the CCT curve to the right side and the decrease of critical martensite formation cooling rate. The CSBW possesses the highest microhardness value in the weld metal due to the existence of the martensite zone. The impact tests were carried out and the results showed that the Charpy absorbed energy of weldments (81 J) is almost equal to that of base clad plate (83 J). The SSCW layer possesses the ductile fracture characteristics accompanying many dimples. However, in the CSBW layer, some cleavage fracture characteristics are presented in the radiation zone while many dimples are located in the fibrous zone, revealing a complex combination of brittle and ductile fracture behavior, which is due to the existence of martensite zone, different stress states and crack propagation velocity. Hybrid (TIG, MAG) welding is suitable for welding stainless steel clad plate; The martensite formation in CSBW is related to dilution and diffusion of Cr and Ni; Partial martensite transformation can strengthen and toughen the welding seam. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the role of microRNA-212-5p (miR-212-5p) in clear cell renal cell carcinoma (ccRCC) and to explore the potential underlying mechanisms. MATERIALS AND METHODS: 32 pairs of ccRCC clinical samples were collected. Renal ccRCC cells (786-O) and embryonic kidney cells (293T) were cultured in vitro. The ability of cell proliferation was detected by 3-(4,5)-dimethylthiazol(- z-y1)-3,5-diphenyl tetrazolium bromide (MTT) assay. Transwell migration assay was used to detect the abilities of cell invasion and migration. The relative protein and mRNA expressions of miR-212-5p were detected by Western blot and quantitative Real-time polymerase chain reaction (qRT-PCR) analysis, respectively. Furthermore, bioinformatics online sites and luciferase reporter gene assay were performed to predict and verify the potential targets of miR-212-5p, respectively. RESULTS: The expression level of miR-212-5p in ccRCC tissues and cell lines was significantly inhibited. Bioinformatics online sites and luciferase reporter gene assay confirmed that T-box transcription factor TBX15 (TBX15) was the potential target gene of miR-212-5p. In vitro experiments demonstrated that the proliferation, cell cycle, cell invasion and migration of ccRCC cells were obviously restricted after up-regulation of miR-212-5p. However, the above functional effects were significantly abolished in ccRCC cells after co-transfection with miR-212-5p mimics and LV-TBX15. CONCLUSIONS: MiR-212-5p acted as a tumor suppressor gene in ccRCC. Through targeting TBX15, miR-212-5p significantly inhibited the malignant behavior of ccRCC cells. Our findings revealed that miR-212-5p/TBX15 axis might be a potential therapeutic target for the treatment of ccRCC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been reported to be vital in tumor progression. Hepatocellular carcinoma (HCC) is a common type of fatal primary liver cancers worldwide. This study aims to determine whether lncRNA SNHG7 (small nucleolar RNA host gene 7) functions in the metastasis of HCC. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the SNHG7 expression in HCC cells and tissue samples. Moreover, function assays were performed in vitro to identify the role of SNHG7 in metastasis of HCC cells. Western blot assay was used to explore the possible mechanism. RESULTS: SNHG7 expression was remarkably higher in HCC tissues than that in adjacent tissues. Moreover, HCC migration and invasion were suppressed after silence of SNHG7 in HCC cells. Moreover, after silence of SNHG7, RBM5 was upregulated in HCC cells. Besides, the expression of RBM5 in tumor tissues was negatively correlated to the expression of SNHG7. CONCLUSIONS: Our study suggests that SNHG7 could promote cell invasion and migration in HCC cells through downregulating RBM5, which may offer a new therapeutic intervention for HCC patients. [ABSTRACT FROM AUTHOR]

To investigate the characteristics of the bubbles trapped in liquid cross flow, air was injected into flowing water circulated in a closed loop. High speed photography was used to record bubble images instantaneously. An image-processing code was specifically developed to identify bubbles in the images and to calculate bubble parameters. Effects of the water velocity and the flow rate of the injected air on bubble patterns were investigated. The results indicate that the inclination of bubble trajectory relative to the nozzle axis is enhanced as the water velocity rises. Meanwhile, bubble size varies inversely with the water velocity. The bubble profile tends to be rounded as the water velocity increases. Fluctuations of the bubble velocity are intensified as the water velocity decreases. As the balance between the external forces exerted on the bubble is reached, an approximately linear relationship between the velocities of the bubble and the water is manifested. For a given equivalent bubble diameter, the bubble terminal velocity is higher than that associated with quiescent water. At small Eötvös number, the consistency of the bubble aspect ratio in the liquid flow and quiescent water is revealed. The range of Eötvös number is extended considerably due to the flowing water. Values of Weber number are accumulated in a range within which high bubble aspect ratio is associated with relatively high water velocity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the expression level of microRNA-485-5p (miRNA-485-5p) in acute myeloid leukemia (AML) and its biological function in regulating the proliferative ability of AML through targeting SALL4. PATIENTS AND METHODS: Serum level of miRNA-485-5p in AML patients and healthy controls was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). MiRNA-485-5p level in AML cell lines was detected by qRT-PCR as well. Proliferative and apoptotic changes in AML5 and U937 cells overexpressing miRNA-485-5p were assessed. Subsequently, the regulatory effect of miRNA-485-5p on SALL4 level was evaluated. Rescue experiments were conducted to uncover the role of miRNA-485-5p/SALL4 regulatory loop in regulating cellular behaviors of AML. RESULTS: Compared with healthy controls, serum level of miRNA-485-5p was lower in AML patients. MiRNA-485-5p was similarly downregulated in AML cell lines. Overexpression of miRNA-485-5p stimulated proliferation and alleviated apoptosis in AML. SALL4 level was downregulated by transfection of miRNA-485-5p mimics in AML5 and U937 cells. Overexpression of SALL4 could reverse the regulatory effect of miRNA-485-5p on proliferative and apoptotic abilities of AML. CONCLUSIONS: MiRNA-485-5p is downregulated in AML. Overexpression of miRNA-485-5p alleviates the malignant progression of AML through downregulating SALL4. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate the inhibitory role of microRNA- 1299 (miR-1299) in prostate cancer, and to explore the possible underlying mechanism. PATIENTS AND METHODS: The expression of miR-1299 in 35 PCa tissues and para-carcinoma tissues, as well as PCa cell lines (PC-3) and prostatic epithelial cell line (RWPE-1), was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, we explored the possible targets of miR-1299 by searching online databases. NIMA-related kinase 2 (NEK2) was identified as a direct target gene of miR-1299. Subsequently, qRT-PCR, Western blot (WB), and luciferase reporter gene assay were used to further verify the correlation between miR-1299 and NEK2. To better characterize the role of miR-1299 and NEK2 in PCa, we conducted functional experiments (MTT, flow cytometry, scratch-wound, and transwell assay) by transfecting PC-3 cells with miR-1299 mimics and si- NEK2 in different groups. RESULTS: The expression level of miR-1299 in PCa tissues was significantly lower than that of para-carcinoma tissues. Meanwhile, the expression of miR-1299 in PC-3 cells was also significantly downregulated when compared with RWPE-1 cells. Subsequent qRT-PCR, WB, and luciferase reporter gene assay verified that miR- 1299 transcriptionally repressed NEK2 by interacting with the essential binding sequence in 3'- UTR. Also, functional experiments demonstrated that decreased expression of NEK2 resulting from miR-1299 up-regulation could remarkably inhibit the proliferation, invasion, and migration of PCa cells. CONCLUSIONS: Our study indicated that miR-1299 was a novel suppressor in PCa through its negative regulation of NEK2. Moreover, our findings revealed that miR-1299/NEK2 axis might be a potential therapeutic target for the treatment of PCa. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To elucidate the biological functions of long non-coding RNA (lncRNA) SNHG7 in breast cancer (BC), and its underlying mechanism in the occurrence and progression of BC. PATIENTS AND METHODS: The expression of SNHG7 in 72 pairs of BC tissues and paracancerous tissues was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Correlation between SNHG7 expressions with pathological indicators of BC patients was analyzed. Similarly, SNHG7 expression in BC cell lines was determined by qRT-PCR as well. After constructing the small inference RNA of SNHG7, cell proliferation, migration and invasion were determined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assay. MicroRNA-186 expression in BC tissues and cells was accessed. Dual-luciferase reporter gene assay was conducted to verify the binding condition between SNHG7 and microRNA-186. RESULTS: SNHG7 expression was higher in BC tissues than that of paracancerous tissues. High expression of SNHG7 was positively correlated to tumor stage, lymph node metastasis and distant metastasis, whereas not correlated to age, sex and tumor location of BC. Kaplan-Meier curves revealed that higher expression of SNHG7 is correlated to the worse prognosis of BC patients. SNHG7 was highly expressed in BC cells as well. Knockdown of SNHG7 inhibited proliferative, invasive and migratory abilities of BC cells. QRT-PCR data showed that microRNA-186 is lowly expressed in BC tissues compared with that of paracancerous tissues. MicroRNA-186 was lowly expressed in BC cells as well. Both mRNA and protein levels of microRNA-186 were negatively correlated to SNHG7 in BC tissues. Finally, the dual-luciferase reporter gene assay demonstrated that SNHG7 could be directly targeted by microRNA-186. CONCLUSIONS: SNHG7 is highly expressed in BC, which is correlated to tumor stage, lymph node metastasis and distant metastasis of BC patients. SNHG7 could promote malignant progression of BC by regulating microRNA-186. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Hepatocarcinoma is a great threat to global health. MicroRNA-23a was suggested to regulate growth and apoptosis in certain cell lines. Our study was focused on growth, proliferation, and apoptosis of hepatocarcinoma cell line MHCC97H under the influence of microRNA-23a, and explored the mechanism of pro-apoptosis microRNA-23a. MATERIALS AND METHODS: MicroRNA-23a and control microRNA (scramble miRNA, for short as miRNA) were synthesized with the routine protocol. Lipofection transfection was performed in hepatocarcinoma cell line MHCC97H. 3-(4,5-dimethyl- 2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, caspase-3 activity detection, and flow cytometry were performed to examine growth, proliferation, and apoptosis of hepatocarcinoma cell line MHCC97H, respectively. Kidney inhibitor of apoptosis protein (KIAP) and small interfere RNA (siRNA) was synthesized for inhibition of KIAP. KIAP plasmid was established for activation of KIAP. Western blot was performed to examine the protein expression of KIAP and caspase protein family after transfection of KIAP siRNA or KIAP plasmid. RESULTS: Compared with miRNA transfection, microRNA-23a transfection significantly reduced the growth of MHCC97H cells, and decreased the expression of KIAP (p < 0.05). Enhanced translocation of phosphatidylserine and activation of caspase-3 were observed in microRNA-23a transfection cells. Moreover, inhibition of KIAP enhanced the pro-apoptosis effect of microRNA-23a, while activation of KIAP abrogated pro-apoptosis effect of microRNA- 23a. CONCLUSIONS: MicroRNA-23a inhibits growth and proliferation of MHCC97H cells, and induces apoptosis of MHCC97H cells via down-regulating KIAP. KIAP could be a potential therapeutic target for hepatocarcinoma treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]