Intranasal neprilysin rapidly eliminates amyloid-beta plaques, but causes plaque compensations: the explanation why the amyloid-beta cascade may fail?

Neurodegenerative brain disorders are a major burden in our society,such as Alzheimer´s disease.In order to repair or prevent such diseases,drugs are designed which enter the brain,but the blood-brain barrier limits their entry and the search for alternative pathways is important.Recently,we reported that intranasal delivery of the amyloid-beta degrading enzyme neprilysin eliminated amyloid-beta plaques in transgenic Alzheimer´s disease mice.This review describes the anatomical structure of the intranasal pathway,explains the intranasal delivery of pure neprilysin,cell-loaded neprilysin(platelets)and collagen-embedded neprilysin to destruct amyloid-beta plaques in Alzheimer´s disease in transgenic APP_SweDI mice and hypothesizes why this may cause compensation and why the amyloid-beta cascade hypothesis may fail.

Isoliquiritigenin regulated ox-LDL through activating the PPAR-γ signaling pathway to stabilize atherosclerosis plaques

Objective:To explore the molecular mechanisms of isoliquiritigenin in stabilizing atherosclerotic plaques by activating PPAR-γsignal pathway to regulate ox-LDL metabolism.Methods:The ApoE-/-mice AS carotid plaque model was prepared by using high fat diet and right perivascular carotid collar placement(PCCP).ApoE-/-mice were randomly divided into the model group and the isoliquiritigenin group after PCCP.C57BL/6J mice were used for the control group.High fat diet continued feeding for 8 weeks after PCCP to establish the AS model.Automatic biochemical analyzer was used to test levels of total cholesterol(TC),triacylglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).ELISA was used to measure oxidized low-density lipoprotein(ox-LDL)in serum.Hematoxylin-eosin(HE)staining was used to observe the pathological pattern of the carotid artery,and then calculated the carotid parameters.Oil red O staining was used for lipid determination,Masson staining was used to determine collagen content,MOMA-2 andα-SMA immunohistochemical staining were used to determine macrophages and smooth muscle cells,and to calculate the vulnerability index.Western blot was used to detected the expression of PPAR-γ,LXR-α,FABP-4,MMP-2 and MMP-9 in mice arteries.Results:Compared with the normal group,TC、TG、LDL-C、HDL-C and ox-LDL were increased in the model group.Compared with the model group,TC、TG、LDL-C and ox-LDL were reduced,and there was no significant change in HDL-C of the isoliquiritigenin group.Compared with the normal group,intima thickness(IT),intima/media thickness(IT/MT),plaque area(PA),and plaque area/lumen area(PA/LA)of carotid arteries were increased,the content of lipid and MOMA-2 in plaques was increased,collagen andα-SMA content decreased,and the vulnerability index was higher in the model group.The expression of PPAR-γand LXR-αwere reduced and the expression of FABP-4,MMP-2 and MMP-9 were increased in the model group.Compared with the model group,carotid IT,IT/MT,PA,and PA/LA were reduced,the content of lipid and MOMA-2 in plaques was decreased,collagen andα-SMA content were increased,and the vulnerability index was decreased in the isoliquiritigenin group.PPAR-γand LXR-αexpression were increased,FABP-4,MMP-2 and MMP-9 expression were decreased significantly in the isoliquiritigenin group.Conclusion:Isoliquiritigenin can exert anti-AS effects by activating PPAR-γ,up-regulating LXR-α,reducing FABP-4 expression,reducing ox-LDL,reducing the protein expression of MMP-2 and MMP-9,decreasing plaque vulnerability index,and increasing plaque stability.

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

Tetramethylpyrazine and paeoniflorin combination(TMP-PF)alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide.Previous studies found that tetramethylpyrazine(TMP)and paeonifl orin(PF)combination(TMP-PF)exerts anti-atherosclerotic effects in vitro.However,whether TMP-PF improves atherosclerosis in vivo needs further exploration.The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^(-/-)mice and explore the related molecule mechanisms.Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels,suppressed vascular endothelial growth factor receptor 2(VEGFR2)and nuclear receptor subfamily 4 group A member 1(NR4A1)expression in aortic tissues,inhibited plaque angiogenesis,reduced plaque areas,and alleviated atherosclerosis in ApoE^(-/-)mice.Also,TMP-PF exhibited a better modulation effect than TMP or PF alone.However,NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF.In conclusion,TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway,indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

Analysis of a New Toothbrushing Technique through Plaque Removal Success

Background/Aims: Determining the levels of oral health and the quality of dental care are fundamental to building concepts of oral health. This study aims to assess toothbrushing techniques using a technical and physical model, clarifying how children and pre-adults learn to brush their teeth. Materials and Methods: Data were recorded from 23 participants, both male and female of various ages, using a proposed electronic toothbrush equipped with X-Y-Z axes pathways. The data, collected before and after training experiments, were processed with MATLAB to generate plots for the three axes. Results: The study revealed that most parameter values, such as Mean Difference Between Amplitudes (MAV, 6.00), Wilson Amplitude (WAMP, 179.419), and Average Amplitude Coupling (AAC, 1.270), decreased from before to after the experiments. Furthermore, the average overall epoch lengths (AVG) showed a 75% reduction in movement amplitude between the two experiments. Conclusion: Dentist observations indicated which brushing methods were acceptable or not. Analytical values suggest that individuals learn the toothbrushing technique effectively, and medical observations clearly demonstrate the success of the proposed method.

Jiaohong pills attenuate neuroinflammation and amyloid-βprotein-induced cognitive deficits by modulating the mitogen-activated protein kinase/nuclear factor kappa-B pathway

Background:Jiaohong pills(JHP)consist of Pericarpium Zanthoxyli(PZ)and Radix Rehmanniae,two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment.However,the precise mechanisms underlying the beneficial effects remain elusive.Here,research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease.Methods:BV-2 cell inflammation was induced by lipopolysaccharide.AD mice were administered amyloid-β(Aβ).Behavioral experiments were used to evaluate learning and memory ability.The levels of nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)were detected using enzymelinked immunosorbent assay(ELISA).The protein expressions of inducible nitric oxide synthase(iNOS)and the phosphorylation level of mitogen-activated protein kinase(MAPK)and nuclear factor kappa-B(NF-κB)were detected using Western blot.Nissl staining was used to detect neuronal degeneration.Results:The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO,IL-1β,TNF-α,and iNOS;increased the expression level of IL-10;and significantly decreased the phosphorylation levels of MAPK and NF-κB.These inhibitory effects were further confirmed in the AD mouse model.Meanwhile,JHP improved learning and memory function in AD mice,reduced neuronal damage,and enriched the Nissl bodies in the hippocampus.Moreover,IL-1βand TNF-αin the cortex were significantly downregulated after JHP administration,whereas IL-10showed increased expression.Conclusions:It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF-κB signaling pathway.

Outcomes of surgical correction of Peyronie’s disease with plaque excision and grafting: Comparison of testicular tunica vaginalis graft versus bovine pericardium graft

Objective:Peyronie’s disease(PD)is an abnormal wound healing in the penile tunica albuginea.After fibrotic plaque excision,different graft materials have been used to repair the defects,but the optimal graft remains unknown.This study aimed to compare the functional outcomes of testicular tunica vaginalis grafts and bovine pericardium grafts in patients with severe PD.Methods:A retrospective comparative study was conducted on 33 PD patients undergoing partial plaque excision and grafting from September 2015 to May 2021.The patients were divided into two groups depending on the type of graft used.For 15 patients in Group B,testicular tunica vaginalis grafts were used to repair the defect,while for 18 patients in Group A,bovine pericardium grafts were used.Data of the patient’s age,comorbidities,sexual function,penile curvature,postoperative complications,need for further treatment,change in penile length,and satisfaction were gathered and compared between the groups.Sexual function was evaluated using the 5-item version of the International Index of Erectile Function(IIEF-5),and a functional less than 20-degree penile curvature after surgery was considered a successful intervention.Results:There was no difference in age,comorbidities,degree of curvature,perioperative IIEF-5,operative time,plaque size,or complication rates.After surgery,a statistically significant improvement in curvature degree(p<0.05)and satisfactory penile appearance(p<0.05)were seen in both groups without any superiority between the two groups(p=0.423 and p=0.840,respectively).With a 30-month follow-up,the IIEF-5 was consistent in both groups,with no statistical significance between the groups(p=0.492).The main change in penile length during the operation was increased and still positive in the last follow-up in both groups without statistical significance(p=0.255 and p=0.101,respectively).Conclusion:Partial plaque excision and corporoplasty with both testicular tunica vaginalis or bovine pericardium grafts are equally effective in treating males with clinically significant PD.

FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

Angiographical and histopathologic study of atherosclerotic plaques in acute myocardial infarction

Objective Compare the morphology of atherosclerotic plaquesmgiographically and histopathologically in acute myocardialmfarction m order to accumulate experience in recognizing plaquerupture and thrombus by angiogrames.Material and methods 16postmortem cases of acute myocardial infarction were studied.The coronary arteries were romoved en block,filled with barium the lumen and ridiographed.Then the arteries wereontinuously insetted and routin HE sections were made.Results 16 cases had plaque ruptures and thrombi.Among the total98 blocks,21 had plaque ruptures on which 20 thrombiccur(95.23%).while the other 777 unrupured blocks had only 2hrombi(0.25%).The difference was significant(p【0.001).Therupture mostly occur on unstable plaques.The ruptured plaqueswith thrombi had different angiographical morphology withunruptured plaques.The former had irregular borders andunraluminal lucencies;while the Iatter had smooth borders and nointraluminal lucencies.Conclusions Plaque ruprure withthrumbus was the major cause of acute myocardial infarction andthe ruptured plaques with thrombus had different angiographicalapperances with unruptured plaques.

Assessment of neovascularization within carotid plaques in patients with ischemic stroke

AIM:To assess neovascularization within human ca-rotid atherosclerotic soft plaques in patients with isch-emic stroke.METHODS:Eighty-one patients with ischemic stroke and 95 patients without stroke who had soft athero-sclerotic plaques in the internal carotid artery were studied.The thickest soft plaque in each patient was examined using contrast-enhanced ultrasound.Time-intensity curves were collected from 5 s to 3 min after contrast injection.The neovascularization within the plaques in the internal carotid artery was evaluated using the ACQ software built into the scanner by 2 of the experienced investigators who were blinded to the clinical history of the patients.RESULTS:Ischemic stroke was present in 7 of 33 patients(21%) with grade Ⅰ plaque,in 14 of 51 pa-tients(28%) with grade Ⅱ plaque,in 26 of 43 patients(61%) with grade Ⅲ plaque,and in 34 of 49 patients(69%) with grade Ⅳ plaque(P < 0.001 comparing grade Ⅳ plaque with grade I plaque and with grade Ⅱ plaque and P = 0.001 comparing grade Ⅲ plaque with grade Ⅰ plaque and with grade Ⅱ plaque).Analysis of the time intensity curves revealed that patients with ischemic stroke had a significantly higher intensity of enhancement(IE) than those without ischemic stroke(P < 0.01).The wash-in time(WT) of plaque was signifi-cantly shorter in stroke patients(P < 0.05).The sensi-tivity and specificity for IE in the plaque were 82% and 80%,respectively,and for WT were 68% and 74%,respectively.There was no significant difference in the peak intensity or time to peak between the 2 groups.CONCLUSION:This study shows that the higher the grade of plaque enhancement,the higher the risk of ischemic stroke.The data suggest that the presence of neovascularization is a marker for unstable plaque.

Value of superb micro-vascular imaging in predicting ischemic stroke in patients with carotid atherosclerotic plaques

BACKGROUND Unstable carotid atherosclerotic plaques are prone to cause ischemic stroke.Contrast-enhanced ultrasound(CEUS) is the primary method of assessing plaque stability, but CEUS cannot be a method for screening for unstable plaque. The emergence of superb micro-vascular imaging(SMI) offers the possibility of clinically screening for unstable plaque AIM To investigate the value of SMI in predicting ischemic stroke in patients with carotid atherosclerotic plaques.METHODS Patients with carotid atherosclerotic plaques(luminal stenosis of 50%-70%) were enrolled into the present study. All patients received conservative medication.The patient's clinical baseline data, serological data, CEUS and SMI data were analyzed. All patients underwent a 3-year follow-up. The follow-up endpoint was the occurrence of ischemic stroke and patients were divided into stroke group and non-stroke group according to whether the prognosis occurred or not.Subsequently, the difference in clinical data was compared, the correlation of SMI and CEUS was analyzed, and multiple Cox regression and receiver operating characteristic curve were applied to investigate the value of SMI and CEUS in predicting cerebral arterial thrombosis in three years.RESULTS In this study, 43 patients were enrolled in the stroke group and 82 patients were enrolled in the non-stroke group. Cox regression revealed that SMI level(P =0.013) and enhancement intensity(P = 0.032) were the independent factors influencing ischemic stroke. There was a positive correlation between SMI level and enhancement intensity(r = 0.737, P = 0.000). The area under curve of SMI level predicting ischemic stroke was 0.878. The best diagnostic point was ≥ level Ⅱ, and its sensitivity and specificity was 86.05% and 79.27%. The area under curve of enhancement intensity predicting ischemic stroke was 0.890. The best diagnostic point was 9.92 db, and its sensitivity and specificity was 88.37% and89.02%. As the SMI level gradually increased, the incidence of ischemic stroke increased gradually(X^2 = 108.931, P = 0.000).CONCLUSION SMI can be used as a non-invasive method of screening for unstable plaques and may help prevent ischemic stroke.

Caries-related factors and bacterial composition of supragingival plaques in caries free and caries active Algerian adults

Objective: To compare oral hygiene practices, education and social background, food intake and oral malodor of Algerian adults suffering from dental caries with normal controls, and to determine and compare the bacterial composition of the supragingival plaques from the above-mentioned groups.Methods: Participants completed a questionnaire and were clinically examined for dental caries using decayed, missing and filled teeth index according to the criteria laid down by the World Health Organization. Supragingival plaque samples were collected from 50 caries-free adults(CF) and 50 caries-active adults(CA). Standard procedures of culture and identification of aerobic and anaerobic bacteria were used. Data were analyzed using Chi-square test.Results: A total of 117 bacterial strains were isolated from supragingival plaques in CF group subjects, 76(64.96%) of them belonged to 9 aerobic genera, and 41(35.04%) to 9anaerobic genera(P < 0.05). While in the second group, 199 strains were isolated, 119(59.80%) of the strains belonged to 10 aerobic genera and 80(40.20%) to 10 anaerobic bacteria(P < 0.05). Streptococcus mutans, Enterococcus faecium, Aerococcus viridans,Actinomyces meyeri, Lactobacillus acidophilus and Eubacterium limosum showed a significantly higher prevalence in the CA group(P < 0.05). The findings revealed that CA group had a high sugar intake(80%). A significantly higher frequency of tooth brushing(P < 0.000) and a significantly less self-reported oral malodor(P < 0.000) and tooth pain(P < 0.000) were found in CF group, while there was no association of socioeconomic levels and intake of meal snacks with dental caries.Conclusions: This study confirms the association of some aciduric bacteria with caries formation, and a direct association of sugar intake and cultural level with dental caries.Furthermore, oral hygiene practices minimize the prevalence of tooth decay.

Automatic Calcified Plaques Detection in the OCT Pullbacks Using Convolutional Neural Networks

Background Coronary artery calcification is a well-known marker of atherosclerotic plaque burden.High-resolution intravascular optical coherence tomography(OCT)imaging has shown the potential to characterize the details of coronary calcification in vivo.In routine clinical practice,it is a time-consuming and laborious task for clinicians to review the over 250 images in a single pullback.Besides,the imbalance label distribution within the entire pullbacks is another problem,which could lead to the failure of the classifier model.Given the success of deep learning methods with other imaging modalities,a thorough understanding of calcified plaque detection using Convolutional Neural Networks(CNNs)within pullbacks for future clinical decision was required.Methods All 33 IVOCT clinical pullbacks of 33 patients were taken from Affiliated Drum Tower Hospital,Nanjing University between December 2017 and December 2018.For ground-truth annotation,three trained experts determined the type of plaque that was present in a B-Scan.The experts assigned the labels'no calcified plaque','calcified plaque'for each OCT image.All experts were provided the all images for labeling.The final label was determined based on consensus between the experts,different opinions on the plaque type were resolved by asking the experts for a repetition of their evaluation.Before the implement of algorithm,all OCT images was resized to a resolution of 300×300,which matched the range used with standard architectures in the natural image domain.In the study,we randomly selected 26 pullbacks for training,the remaining data were testing.While,imbalance label distribution within entire pullbacks was great challenge for various CNNs architecture.In order to resolve the problem,we designed the following experiment.First,we fine-tuned twenty different CNNs architecture,including customize CNN architectures and pretrained CNN architectures.Considering the nature of OCT images,customize CNN architectures were designed that the layers were fewer than 25 layers.Then,three with good performance were selected and further deep fine-tuned to train three different models.The difference of CNNs was mainly in the model architecture,such as depth-based residual networks,width-based inception networks.Finally,the three CNN models were used to majority voting,the predicted labels were from the most voting.Areas under the receiver operating characteristic curve(ROC AUC)were used as the evaluation metric for the imbalance label distribution.Results The imbalance label distribution within pullbacks affected both convergence during the training phase and generalization of a CNN model.Different labels of OCT images could be classified with excellent performance by fine tuning parameters of CNN architectures.Overall,we find that our final result performed best with an accuracy of 90%of'calcified plaque'class,which the numbers were less than'no calcified plaque'class in one pullback.Conclusions The obtained results showed that the method is fast and effective to classify calcific plaques with imbalance label distribution in each pullback.The results suggest that the proposed method could be facilitating our understanding of coronary artery calcification in the process of atherosclerosis andhelping guide complex interventional strategies in coronary arteries with superficial calcification.

Correlation of Enhancement Degree on Contrast-enhanced Ultrasound with Histopathology of Carotid Plaques and Serum High Sensitive C-Reactive Protein Levels in Patients Undergoing Carotid Endarterectomy

This study was undertaken to investigate the correlation of the enhancement degree on contrast-enhanced ultrasound(CEUS) with the histopathology of carotid plaques and the serum high sensitive C-reactive protein(hs-CRP) levels in patients undergoing carotid endarterectomy(CEA). Carotid CEUS was performed preoperatively in 115 patients who would undergo CEA, and the enhancement degree of the carotid plaques was evaluated by both the visual semiquantitative analysis and the quantitative time-intensity curve analysis. Serum hs-CRP levels were detected using the particle-enhanced immunoturbidimetric assay also before the operation. Additionally, the carotid plaque samples were subjected to histopathological examination postoperatively. The density of neovessels and the number of macrophages in the plaques were assessed by immunohistochemistry. The results showed that among the 115 patients, grade 0 plaque contrast enhancement was noted in 35 patients, grade 1 in 48 patients and grade 2 in 32 patients. The degree of plaque enhancement, the density of neovessels, the number of macrophages, and the hs-CRP levels were highest in the grade 2 patients. Correlation analysis showed that the enhancement degree of the carotid plaques was closely related to the immunohistochemical parameters of the plaques and the serum hs-CRP levels. It was suggested that the carotid plaque enhancement on CEUS can be used to evaluate the vulnerability of carotid plaques.

Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques

Background Atherosclerotic plaques indicate the occurrence of ischemia events and it is a difficult task for clinical physicians. Grape seed proanthocyanidin extract （GSPE） has been reported to exert an antiatherogenic effect by inducing regression of atherosclerotic plaques in animal experimental studies. In this study, the antiatherogenic effect of GSPE has been investigated in clinical use. Methods Consecu- tive 287 patients diagnosed with asymptomatic carotid plaques or abnormal plaque free carotid intima-media thickness （CIMT） were ran- domly assigned to the GSPE group （n = 146） or control group （n = 141）. The patients in the GSPE group received GSPE 200 mg per day orally, while patients in the control group were only enrolled in a lifestyle intervention program. Carotid ultrasound examination was per- formed at baseline and 6, 12, 24 months during follow-up. Mean maximum CIMT （MMCIMT）, plaque score, echogenicity of plaques and ischemic vascular events were recorded. Results As anticipated, after treatment, GSPE resulted in significant reduction in MMCIMT pro- gression （4.2% decrease after six months, 4.9% decrease after 12 months and 5.8% decrease after 24 months） and plaque score （10.9% de- crease after six months, 24.1% decrease after 12 months and 33.1% decrease after 24 months） for the primary outcome, while MMCIMT and plaque score were stable and even increased with the time going on in control group. The number of plaques and unstable plaques also de- creased after treatment of GSPE. Furthermore, the carotid plaque can disappear after treatment with GSPE. The incidence rate for transitory ischemic attack （TIA）, arterial revascularization procedure, and hospital readmission for unstable angina in GSPE group were statistically significant lower （P = 0.02, 0.08, 0.002, respectively） compared with the control group. Conclusions GSPE inhibited the progression of MMCIMT and reduced carotid plaque size in GSPE treated patients, and with extended treatment, the superior efficacy on MMCIMT and carotid plaque occurred. Furthermore, the GSPE group showed lower rates of clinical vascular events.

Subclinical hypothyroidism is associated with lipid-rich plaques in patients with coronary artery disease as assessed by optical coherence tomography

Background Subclinical hypothyroidism （SCH） has recently been acknowledged as an unconventional risk factor for coronary artery disease （CAD） and characterized by poor prognosis, which may be due to atherosclerotic plaque characteristics. We conducted this study to observe coronary plaque characteristics in coronary artery disease patients with concomitant SCH. Methods Patients with coronary artery disease were enrolled in the study and divided into an SCH group （patients, n = 26; plaques, n = 35） and a non-SCH group （patients, n = 52; plaques, n = 66）. They were divided 1：2 according to propensity-matched analysis including age, diabetes mellitus, gender, CAD severity and culprit vessel. Optical coherence tomography （OCT） imaging was performed on all patients, and images were analyzed by two inde- pendent investigators. Lipid-rich plaques （LRP）, the precursor of vulnerable plaques, were defined as having more than one quadrant occu- pied with lipid pool. Maximum lipid arcs were simultaneously recorded. Fibrotic plaques and calcific plaques were also identified. The pres- ence of coronary dissection, plaque erosion, thrombus, macrophage, calcific nodule, thin-cap fibroatheroma and micro channel were all noted. Results The ratio of LRP in SCH group was significantly higher than that in non-SCH group （54% vs. 30.3%, P = 0.037）. That was the case as well for the maximum lipid arcs value （181.5°± 61.6° vs. 142.1° 4± 35.9°, p = 0.046）. While thin-cap fibroatheroma （TCFA） was detected, no difference was identified between the two groups in either TCFA ratio （20% vs. 16.7%, P = 0.579） or fibrous cap thickness （57.5 4± 14.0 vs. 63.5 4±10.7 gin, P = 0.319）. Other OCT characteristics such as dissection, plaque erosion, thrombus, macrophage shadow and calcific nodule were also similar. ConcLusion Higher ratio of LRP with greater lipid arc in SCH patients may be related to the plaque instability and poor prognosis in CAD patients with SCH.

Study of Helicobacter pylori genotype status in saliva,dental plaques,stool and gastric biopsy samples

AIM:To compare genotype of Helicobacter pylori(H.pylori) isolated from saliva,dental plaques,gastric biopsy,and stool of each patient in order to evaluate the mode of transmission of H.pylori infection.METHODS:This cross-sectional descriptive study was performed on 300 antral gastric biopsy,saliva,dental plaque and stool samples which were obtained from patients undergoing upper gastrointestinal tract endoscopy referred to endoscopy centre of Hajar hospital of Shahrekord,Iran from March 2010 to February 2011.Initially,H.pylori strains were identified by rapid urease test(RUT) and polymerase chain reaction(PCR) were applied to determine the presence of H.pylori(ureC) and for genotyping of voculating cytotoxin gene A(vacA) and cytotoxin associated gene A(cagA) genesin each specimen.Finally the data were analyzed by using statistical formulas such as Chi-square and Fisher's exact tests to find any significant relationship between these genes and patient's diseases.P < 0.05 was considered statistically significant,RESULTS:Of 300 gastric biopsy samples,77.66% were confirmed to be H.pylori positive by PCR assay while this bacterium were detected in 10.72% of saliva,71.67% of stool samples.We were not able to find it in dental plaque specimens.The prevalence of H.pylori was 90.47% among patients with peptic ulcer disease(PUD),80% among patients with gastric cancer,and 74.13% among patients with none ulcer dyspepsia(NUD) by PCR assay.The evaluation of vacA and cagA genes showed 6 differences between gastric biopsy and saliva specimens and 11 differences between gastric and stool specimens.94.42% of H.pylori positive specimens were cagA positive and all samples had amplified band both for vacA s and m regions.There was significant relationship between vacA s1a/m1a and PUD diseases(P = 0.04),s2/m2 genotype and NUD diseases(P = 0.05).No statically significant relationship was found between cagA status with clinical outcomes and vacA genotypes(P = 0.65).The evaluation of vacA and cagA genes showed 6 differences between gastric biopsy and saliva specimens and 11 differences between gastric and stool specimens,CONCLUSION:Regard to high similarity in genotype of H.pylori isolates from saliva,stomach and stool,this study support the idea which fecal-oral is the main route of H.pylori transmission and oral cavity may serve as a reservoir for H.pylori,however,remarkable genotype diversity among stomach,saliva and stool samples showed that more than one H.pylori genotype may exist in a same patient.

Significance of Increased CIMT with Coexisting Carotid Plaques in Cerebral White Matter Lesions in Elders

It is very common that increased carotid intima media thickness （CIMT） and carotid plaque coexist in a single subject in elderly patients with white matter lesions （WMLs）. In this study we inves- tigated whether the coexistence of increased CIMT and carotid plaque is more strongly associated with the presence and extent of WMLs than either alone. All patients were classified into 1 of the following 4 groups： without either increased CIMT （I） or carotid plaque （P）： I（-）P（-）; with only increased CIMT： I（＋）P（-）; with only carotid plaque： I（-）P（＋）; and with both increased CIMT and carotid plaque： I（＋）P（＋） The presence and severity of periventricular WMLs （PWMLs） and deep WMLs （DWMLs） were as- sessed and the prevalence of MRI findings by the Cochran-Armitage trend test was calculated. The characteristics of subjects showed that the percentages of patients with increased CIMT and carotid plaque in the DWMLs group and the PWMLs group were significantly higher than those without WMLs group. Both DWMLs and PWMLs were strongly associated with age, carotid plaque and CIMT. Furthermore, the Cochran-Armitage trend test indicated that the prevalence of MRI findings of PWMLs and DWMLs increased in the order of I（-）P（-）〈 I（＋）P（-）〈 I（-）P（＋）〈 I（＋）P（＋） （P〈0.0001）. For the pa- tients with DWMLs, the grades of both I（＋）P（-） and I（＋）P（＋） were increased significantly compared to I（-）P（-） （P〈0.0025, P〈0.05, respectively） without such a difference found in patients with PWMLs. Our results suggested that the coexistence of increased CIMT and carotid plaque is most closely associated with WMLs, and that increased CIMT is associated with the severity of DWMLs, whereas carotid plaque is related to the presence of WMLs.

Effects of different statins application methods on plaques in patients with coronary atherosclerosis

BACKGROUND Discontinued application of statins may be related to adverse cardiovascular events.However,it is unclear whether different statins administration methods have effects on coronary artery plaques.AIM To evaluate the effects of different statins application methods on plaques in patients with coronary atherosclerosis.METHODS A total of 100 patients diagnosed with atherosclerotic plaque by coronary artery computed tomography were continuously selected and divided into three groups according to different statins administration methods(discontinued application group,n=32;intermittent application group,n=39;sustained application group,n=29).The effects of the different statins application methods on coronary atherosclerotic plaque were assessed.RESULTS The volume change and rate of change of the most severe plaques were significantly reduced in the sustained application group(P≤0.001).The volume change of the most severe plaques correlated positively with low-density lipoprotein(LDL-C)levels only in the sustained application group(R=0.362,P=0.013).There were no changes in plaques or LDL-C levels in the intermittent and discontinued application groups.CONCLUSION Continuous application of statins is effective for controlling plaque progression,whereas discontinued or intermittent administration of statins is not conducive to controlling plaques.Only with continuous statins administration can a reduction in LDL-C levels result in plaque volume shrinkage.