Research Progress of Coronary Physiological Evaluation Development in 2021 / 医用生物力学

Cardiovascular disease is one of the most serious diseases endangering human life and health. In China, 2 out of every 5 people die of cardiovascular diseases. Myocardial ischemia is one of the important cardiovascular diseases. Fractional flow reserve (FFR) is used to quantify myocardial ischemia in epicardial stenoses. Index of microvascular resistance (IMR) is an invasive index for quantitative evaluation of coronary microcirculation. Traditional FFR and IMR measurements rely on guide wires to perform interventional measurements under the maximum hyperemia state,so as to assist the diagnosis of myocardial ischemia clinically. Coronary angiography-derived FFR and IMR without using invasive pressure-wire measurement, hyperemic stimulus and contraindications can assist the diagnosis and treatment of percutaneous coronary intervention by fast simultaneous calculation of FFR and IMR. In this review, the research progress of coronary angiography-derived FFR and IMR as well as other coronary physiological evaluation in recent years were summarized. It is of great clinical value to further study the combination of coronary angiography-derived FFR and IMR in functional research of coronary circulation from macro to micro.

Index of microcirculatory resistance: state-of-the-art and potential applications in computational simulation of coronary artery disease / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The dysfunction of coronary microcirculation is an important cause of coronary artery disease (CAD). The index of microcirculatory resistance (IMR) is a quantitative evaluation of coronary microcirculatory function, which provides a significant reference for the prediction, diagnosis, treatment, and prognosis of CAD. IMR also plays a key role in investigating the interaction between epicardial and microcirculatory dysfunctions, and is closely associated with coronary hemodynamic parameters such as flow rate, distal coronary pressure, and aortic pressure, which have been widely applied in computational studies of CAD. However, there is currently a lack of consensus across studies on the normal and pathological ranges of IMR. The relationships between IMR and coronary hemodynamic parameters have not been accurately quantified, which limits the application of IMR in computational CAD studies. In this paper, we discuss the research gaps between IMR and its potential applications in the computational simulation of CAD. Computational simulation based on the combination of IMR and other hemodynamic parameters is a promising technology to improve the diagnosis and guide clinical trials of CAD.

Autopsy-based morphometric study of coronary atherosclerosis in young adults

Background & objectives: The burden of cardiovascular diseases is high in Kerala, India, and a considerable proportion of these occur in young people. The objective of this study was to estimate the severity of atherosclerosis in autopsies done for accidental and suicidal deaths in victims below 40 yr of age. Methods: Coronary arteries from 77 autopsies done for unnatural deaths in a population below 40 yr were graded, and the degree of stenosis, intimal thickness index (ITI) and the intima-media ratio (IMR) were measured. Results: There were 65 males and 12 females in the sample. The American Heart Association (AHA) type 3-6 (pathological intimal thickening) was seen in 55.4 per cent [95% confidence interval (CI): 42.5-67.7%] of males and 25 per cent (95% CI: 5.5-57.2%) of females and advanced lesions (type 4-6) in 44.6 per cent (95% CI: 32.3-57.5%) of males and 8.3 per cent (95% CI: 0.2-38.5%) of females. Types 5 or 6 lesions were seen in 32.2 per cent (95% CI: 21.2-45.1%) of males. The mean stenosis was 57.3 per cent in males and 40.6 per cent in females. More than 40 per cent stenosis was seen in 76.6 per cent cases, more than 50 per cent in 54.5 per cent cases and more than 75 per cent stenosis in 14.3 per of the sample. The mean ITI (MIT) was 1.85 and the mean IMR was 4.11. The degree of stenosis, MIT and IMR were significantly associated with male sex, overweight and smoking. Interpretation & conclusions: Morphometric data showed that the degree of atherosclerotic narrowing of coronary arteries in young non-diseased population was high. It portends a danger to the community unless preventive measures are taken up.

Study on the Effects of Tetrandrine on Proliferation and Migration ，Invasion Ability of Neuroblastoma Cells and Its Mechanism / 中国药房

OBJECTIVE： To investigate the effects of tetrandrine （TET） on the proliferation and migration， invasion ability of neuroblastoma cells and its mechanism. METHODS： Human neuroblastoma cell lines IMR-32 and SH-SY5Y were chosen as objects. MTT assay was used to detect the effects of 0 （blank control）， 2.5， 5， 10， 15， 20 μmol/L TET on cell proliferation. The transmembrane number of normal control group （TET concentration of 0 μmol/L） and TET group （10 μmol/L for IMR-32 cells， 15 μmol/L for SH-SY5Y cells） were investigated by Transwell cell migration and invasion experiments. The protein levels of MMP-2， MMP-9， β-catenin， GSK3β and p-GSK3β in IMR-32 cells and SH-SY5Y cells were tested by Western blotting assay after treated with TET of above concentrations. RESULTS： TET with 5， 10， 15， 20 μmol/L can reduce the survival rate of IMR-32 cells and SH-SY5Y cells significantly （P＜0.05 or P＜0.01）. IC50 of which to IMR-32 cells and SH-SY5Y cells were 10.148 and 14.461 μmol/L， respectively. Results of migration and invasion experiments showed that compared with normal control group， the number of transmembrane cells was decreased significantly in TET group （P＜0.01）. Results of Western blotting assay showed that compared with normal control group， the protein expression levels of MMP-2，MMP-9，β-catenin and p-GSK3β were decreased significantly in TET group （P＜0.01）. CONCLUSIONS： TET shows significant inhibitory effects on the proliferation， migration and invasion ability of neuroblastoma cells， the mechanism of which may be associated with down-regulating the protein expression of MMP-2 and MMP-9 and inhibiting Wnt/β-catenin signaling pathway.

Bacopa monnieri extracts prevent hydrogen peroxide-induced oxidative damage in a cellular model of neuroblastoma IMR32 cells / 中国天然药物

Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide (HO), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against HO induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri (BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against HO-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.

Does Pre-Treatment with High Dose Atorvastatin Prevent Microvascular Dysfunction after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome?

BACKGROUND AND OBJECTIVES: There is controversy surrounding whether or not high dose statin administration before percutaneous coronary intervention (PCI) decreases peri-procedural microvascular injury. We performed a prospective randomized study to investigate the mechanisms and effects of pre-treatment high dose atorvastatin on myocardial damage in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing PCI. SUBJECTS AND METHODS: Seventy seven patients with NSTE-ACS were randomly assigned to either the high dose group (atorvastatin 80 mg loading 12 to 24 h before PCI with a further 40 mg loading 2 h before PCI, n=39) or low dose group (atorvastatin 10 mg administration 12 to 24 h before PCI, n=38). Index of microcirculatory resistance (IMR) was measured after stent implantation. Creatine kinase-myocardial band (CK-MB) and high sensitivity C-reactive protein (CRP) levels were measured before and after PCI. RESULTS: The baseline characteristics were not different between the two patient groups. Compared to the low dose group, the high dose group had lower post PCI IMR (14.1±5.0 vs. 19.2±9.3 U, p=0.003). Post PCI CK-MB was also lower in the high dose group (median: 1.40 ng/mL (interquartile range [IQR: 0.75 to 3.45] vs. 4.00 [IQR: 1.70 to 7.37], p=0.002) as was the post-PCI CRP level (0.09 mg/dL [IQR: 0.04 to 0.16] vs. 0.22 [IQR: 0.08 to 0.60], p=0.001). CONCLUSION: Pre-treatment with high dose atorvastatin reduces peri-PCI microvascular dysfunction verified by post-PCI IMR and exerts an immediate anti-inflammatory effect in patients with NSTE-ACS.

Does Pre-Treatment with High Dose Atorvastatin Prevent Microvascular Dysfunction after Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome?

BACKGROUND AND OBJECTIVES: There is controversy surrounding whether or not high dose statin administration before percutaneous coronary intervention (PCI) decreases peri-procedural microvascular injury. We performed a prospective randomized study to investigate the mechanisms and effects of pre-treatment high dose atorvastatin on myocardial damage in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) undergoing PCI. SUBJECTS AND METHODS: Seventy seven patients with NSTE-ACS were randomly assigned to either the high dose group (atorvastatin 80 mg loading 12 to 24 h before PCI with a further 40 mg loading 2 h before PCI, n=39) or low dose group (atorvastatin 10 mg administration 12 to 24 h before PCI, n=38). Index of microcirculatory resistance (IMR) was measured after stent implantation. Creatine kinase-myocardial band (CK-MB) and high sensitivity C-reactive protein (CRP) levels were measured before and after PCI. RESULTS: The baseline characteristics were not different between the two patient groups. Compared to the low dose group, the high dose group had lower post PCI IMR (14.1±5.0 vs. 19.2±9.3 U, p=0.003). Post PCI CK-MB was also lower in the high dose group (median: 1.40 ng/mL (interquartile range [IQR: 0.75 to 3.45] vs. 4.00 [IQR: 1.70 to 7.37], p=0.002) as was the post-PCI CRP level (0.09 mg/dL [IQR: 0.04 to 0.16] vs. 0.22 [IQR: 0.08 to 0.60], p=0.001). CONCLUSION: Pre-treatment with high dose atorvastatin reduces peri-PCI microvascular dysfunction verified by post-PCI IMR and exerts an immediate anti-inflammatory effect in patients with NSTE-ACS.

Feasibility study of contrast-enhanced hepatic CT with low tube voltage using iterative model reconstruction technique / 中华放射医学与防护杂志

Objective To investigate the feasibility of contrast-enhanced CT with low tube voltage using iterative model reconstruction (IMR) technique.Methods Sixty patients were randomly assigned into 2 groups (group A and group B, 30 each) according to random number table.All patients underwent contrast-enhanced hepatic CT.Group A was scanned with 100 kV at arterial phase(AP) and 120 kV at portal vein phase (PVP), while group B was scanned with 120 kV at AP and 100 kV at PVP.All protocols were performed at the same tube current of 250 mAs.Raw data were reconstructed with IMR for AP images in group A and PVP images in group B;and reconstructed with FBP for AP images in group B and PVP images in group A.Images of 4 different groups were obtained: A1(AP,100 kV,IMR) , B1(AP,120 kV, FBP), A2(PVP, 120 kV,FBP) and B2(PVP, 100 kV, IMR).Subjective evaluation indexes for image quality including low-contrast detectability, lesion edge sharpness, image distortion and diagnostic confidence.Objective evaluation indexes included CT attenuation of hepatic parenchyma, image noise, SNR and CNR, which were assessed and compared between groups A1 and B1, groups A2 and B2.Effective radiation doses were calculated.Results Effective dose in group A1 was reduced 35.1％ compared toB1 (t=ll.05, P＜0.01), while a reduction of 37.7％ in group B2 compared to A2 (t=11.64,P ＜ 0.01).Subjective image quality score of low-contrast detectability and lesion edge sharpness were significantly higher in group A1 compared to B1 (Z =6.391, 3.200, P ＜ 0.01), as well as in group B2 compared to A2 (Z =6.559, 3.409, P ＜ 0.01).No differences were found in image distortion and diagnostic confidence between groups A1 and B1, groups A2 and B2, respectively (P ＞ 0.05).Significantly lower image noise and higher SNR/CNR were found in group A1 compared to group B1 (t =12.889, 15.458, 1.325, P ＜ 0.01) , as well as in group B2 compared to group A2(t =15.163, 15.308, 3.136, P ＜0.01).Conclusions Significant radiation dose reduction and image quality improvement in contrast-enhanced hepatic CT can be reached by using low tube voltage protocol combining with IMR technique.

Neuroprotective Effect of Convolvulus pluricaulis Methanol Extract on Hydrogen Peroxide Induced Oxidative Stress in Human IMR32 Neuroblastoma Cell Line.

Aims: The present study aimed to evaluate and ascertain the protective role of methanolic/ethanolic/water extracts of Convolvulus pluricaulis against H2O2 induced cytotoxicity in IMR32 Neuroblastoma cell line as model system and identify the factor responsible for the protective effect. Study Design: Experimental study. Place and Duration of Study: Department of Molecular Biology and Biochemistry, Guru Nanak Dev University, Amritsar & Department of Biotechnology, DAV College, Amritsar, PuCPab, between August 2010 and March 2012. Methodology: Firstly, cytotoxic dose of H2O2 and non-toxic dose of methanolic, ethanolic and water extracts of C. pluricaulis (CP-MEx, CP-EEx and CP-WEx respectively) was determined by MTT assay. Protective effect of CP-MEx, CP-EEx and CP-WEx was determined using quercetin as a positive control. The expression of IMR32 cytoskeletal marker, Neurofilament (NF-200) and stress markers, Heat shock protein (HSP70) and (glucose regulated protein 75, Grp75) Mortalin studied by immunofluorescence and RTPCR results. The level of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, direct scavenger of free radicals, Glutathione and lipid peroxidation were analysed by their standard procedures. Results: The results showed that quercetin, CP-MEx, CP-EEx and CP-WEx displayed cytoprotective activity in IMR32 cells. Out of tested extracts CP-MEx significantly decreased hydrogen peroxide-induced cell death. Significant decrease in NF-200, HSP70 and Mortalin expression was observed in CP-MEx+H2O2 treated cultures as compared to H2O2 treated. Catalase, superoxide dismutase, glutathione peroxidase, Glutathione levels significantly increased in Quercetin and CP-MEx treated cultures. Lipid peroxidation was significantly decreased in both Quercetin and CP-MEx treated cultures. Conclusions: The present work establishes the protective effect of CP-MEx on IMR 32 Human Neuroblastoma cell line which is as much as by quercetin. The cytoprotective effect of CP-MEx was due to induction of antioxidant machinery of the cell hence holds therapeutic value in the treatment and/or prevention of neurodegenerative disorders of oxidative stress.

Intraocular Injection of Muscimol Induces Illusory Motion Reversal in Goldfish

Induced activation of the gamma-aminobutyric acidA (GABA(A)) receptor in the retina of goldfish caused the fish to rotate in the opposite direction to that of the spinning pattern during an optomotor response (OMR) measurement. Muscimol, a GABA(A) receptor agonist, modified OMR in a concentration-dependent manner. The GABA(B) receptor agonist baclofen and GABA(C) receptor agonist CACA did not affect OMR. The observed modifications in OMR included decreased anterograde rotation (0.01~0.03 micrometer), coexistence of retrograde rotation and decreased anterograde rotation (0.1~30 micrometer) and only retrograde rotation (100 micrometer~1 mM). In contrast, the GABA(A) receptor antagonist bicuculline blocked muscimolinduced retrograde rotation. Based on these results, we inferred that the coding inducing retrograde movement of the goldfish retina is essentially associated with the GABA(A) receptor-related visual pathway. Furthermore, from our novel approach using observations of goldfish behavior the induced discrete snapshot duration was approximately 573 ms when the fish were under the influence of muscimol.

Population, health and nutrition in central India: A situational analysis

India is the second most populous in the world, having crossed the population mark of 1 billion in the year 2000. The different geographical regions exhibit different levels of health and nutritional status. Out of 35 states, some are identified as demographically lagging behind, called BIMARU. Central India falls in this category and the present paper provides a situational analysis of the region with respect to population growth, socio-economic condition, health scenario and level of nutrition in the region. The level of socio-economic development is relatively poor in this part when compared to other parts of the country. The population growth is higher than the national average. The Infant mortality rate (IMR) continues to be higher in Central India, varying from 70 to 164 across the districts in the region. Regression analysis shows a negative correlation between Human development index (HDI) and infant mortality rate. Considering 18.5 as a cut-off point for screening the individuals into normal and chronic energy deficiency (CED) groups, it is found that the prevalence of CED is lower among the populations of non-backward districts (50.5 %) than that in the backward districts (53.6 %). It is suggested that the overall socio-economic development should be accelerated and infant mortality controlled in order to improve the health and nutritional status of the people in Central India.

The mechanism of t-butylhydroperoxide-induced apoptosis in IMR-32 human neuroblastoma cells

Apoptosis has been implicated in the pathophysiological mechanisms of various neurodegenerative diseases. In a variety of cell types, oxidative stress has been demonstrated to play an important role in the apoptotic cell death. However, the exact mechanism of oxidative stress-induced apoptosis in neuronal cells is not known. In this study, we induced oxidative stress in IMR-32 human neuroblastoma cells with tert-butylhydroperoxide (TBHP), which was confirmed by significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity. TBHP induced decrease in cell viability and increase in DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. TBHP also induced a sustained increase in intracellular Ca2+ concentration, which was completely prevented either by EGTA, an extracellular Ca2+ chelator or by flufenamic acid (FA), a non-selective cation channel (NSCC) blocker. These results indicate that the TBHP-induced intracellular Ca2+ increase may be due to Ca2+ influx through the activation of NSCCs. In addition, treatment with either an intracellular Ca2+ chelator (BAPTA/AM) or FA significantly suppressed the TBHP-induced apoptosis. Moreover, TBHP increased the expression of p53 gene but decreased c-myc gene expression. Taken together, these results suggest that the oxidative stress-induced apoptosis in neuronal cells may be mediated through the activation of intracellular Ca2+ signals and altered expression of p53 and c-myc.

Construction and Analysis of Painting Probe for Homogeneously Staining Regions in Human Neuroblastoma Cell line IMR-32

Painting probe for HSRs in IMR-32 Neuroblastoma, a pediatric malignant neoplasm of neural crest origin, has a wide range of clinical virulence. The mechanisms contributing to the development of neuroblastomas are largely unclear, but non-random chromosomal changes identified over the past years suggest the involvement of genetic alterations. Amplification of the human N-myc proto-oncogene is frequently seen either in extrachromosomal double minutes or in homogeneously staining regions(HSRs) of aggressively growing neuroblastomas. N-myc maps to chromosome 2 band 24, but HSR have never been observed at this band, suggesting transposition of N-myc during amplification. We have constructed and analyzed the region-specific painting probe for HSR in neuroblastoma IMR-32 to determine the derivative chromosomes. Microdissection was performed on HSR using an inverted microscope with the help of microglass needles and an micromanipulator. We pretreated the microdissected fragments with Topoisomerase I which catalyzes the relaxation of supercoiled DNA, and performed two initial rounds of DNA synthesis with T7 DNA polymerase followed by conventional PCR to enable the reliable preparation of Fluorescent in situ hybridization probe from a single microdissected chromosome. With this method, it was possible to construct the region-specific painting probe for HSR. The probe hybridized specifically to the HSRs of IMR-32, and to 2p24, 2p13 of normal chromosome. Our results suggest there was coamplification of N-myc together with DNA of the chromosome 2p24 and 2p13. Moreover, the fluorescent signals for the amplified chromosomal regions in IMR-32 cells were also easily recognized at a Thus this painting probe can be applied to detect the similar amplification of N-myc in neuroblastoma tissue, and the probe pool for HSR may be used to identify the cancer-relevant genes.

The role of eucaryotic cell surface glycoconjugates in DNA replication.

Multiple forms of ricin have been isolated from castor bean seeds. Two forms, ricin-1 and ricin-2, differ in their isoelectric pI values and toxicity towards IMR- 32 cells. Inhibition of IMR-32 DNA polymerase α2 is more pronounced with ricin-1 (65%) than with ricin-2 (10%). Ricin Β chain (pI = 5.2) isolated from ricin-1 binds to IMR-32 cell surfaces as well as inhibits DNA polymerase α2 activity when studied in vitro. The presence of galβ-linked glycoconjugates near the active site of IMR-32 DNA polymerase α2 has been proposed. Replication modulators which bind to the glycose portion of the enzymes involved in the replication system may need a mandatory binding to cell surface glycoconjugates for their activity.