PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Bioinformatics analysis reveals the potential role of matrix metalloproteinases in immunity and urolithiasis.

Background: The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall's plaques (RPs) begin as interstitial calcium phosphate crystal deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation. Methods: The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs. In vitro experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA. Results: Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs. In vitro validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis. Conclusion: We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.

Characteristics and influencing factors of soil preferential flow in typical stands of Karst area in southwest China.

The study of preferential flow phenomena in Karst areas and the identification of the main factors influencing preferential flow are of great importance for the recovery of local vegetation. The distribution of the dyeing solution in the vertical and horizontal directions was examined by field staining tracer test and image processing technique. We analyzed the total dyeing area ratio, matrix flow depth, preferential flow ratio, and length index as pre-ferential flow characteristic parameters, and 14 factors affecting preferential flow using grey correlation analysis. The results showed that there were two main types of preferential flow, funnel-shaped and dendritic, with lateral water movement occurring in the soil of typical Karst stands. The mean value of the dyeing area ratio of the understory in Karst areas was 19.4%, and that of the matrix flow depth, preferential flow ratio, and length index was 4.96 cm, 62.9%, and 385.5%, respectively. Among the 14 environmental factors influencing preferential flow, the initial soil moisture content had the strongest influence on the dyeing area ratio, the available potassium content had the most significant influence on the matrix flow depth, and available phosphorous content had the most significant influence on both the preferential flow ratio and the length index. The high degree of development and spatial variability of preferential flow under typical forest stands in Karst areas was strongly influenced by physical properties such as initial soil water content, while soil nutrient also exerts important influence on preferential flow.

Relationship between Coronary Artery Tortuosity and Cardiorespiratory Fitness in Patients without Obstructed Coronaries.

OBJECTIVE: This study aimed to analyze the relationship between cardiorespiratory fitness (CRF) and the increasing severity of coronary artery tortuosity (CAT) in patients with non-stenosed coronaries. METHODS: A total of 396 patients who underwent coronary angiography and cardiopulmonary exercise testing (CPET) between August 2020 and July 2021 were included in this single-center retrospective study after excluding patients with significant coronary artery disease (≥50% stenosis). Patients were divided into two groups: no or mild coronary artery tortuosity (N/M-CAT) and moderate to severe coronary artery tortuosity (M/S-CAT) and laboratory electrocardiographic, echocardiographic, and CPET parameters were compared between two groups. RESULTS: M/S-CAT was found in 46.9% of the study participants, with 66.7% being women. M/S-CAT was significantly associated with advanced age (P=0.014) and females (P=0.001). Diastolic dysfunction parameters, E velocity (P=0.011), and E/A ratio (P=0.004) also revealed significant differences between the M/S-CAT group and N/M-CAT group. VO2@peak (1.22±0.39 vs. 1.07±0.39, P<0.01) and VO2@AT (0.77±0.22 vs. 0.71±0.21, P=0.017) were significantly lower in the M/S-CAT group than in the N/M-CAT group. Multivariate logistic regression analysis identified females (OR=0.448; 95% CI, 0.296-0.676; P=0.000) and E/A ratio (OR=0.307; 95% CI, 0.139-0.680; P=0.004) to be independent risk factors of M/S-CAT and showed no association of CPET parameters to M/S-CAT. CONCLUSION: The results indicate that increasing severity of CAT is strongly associated with female gender and E/A ratio and is not directly correlated with decreasing CRF. Further research with a larger patient population and a longer follow-up time is required to fully comprehend the impact of CAT on CRF.

How phosphorylation of RBCs band 3 protein affects storage quality of suspended red blood cells prepared from Tibetan high Hb population / 中国输血杂志

【Objective】 To investigate the quality changes of suspended red blood cells (SRBCs) prepared from the blood of Tibetan high Hb population, and explore the availability and safety of blood collected from Tibetan high Hb population. 【Methods】 The voluntary blood donors were grouped according to the Hb concentration at the initial screening: female blood donors from Tibet Autonomous Region (>3 500 m) with Hb≥190 g/L and male blood donors with Hb≥210 g/L were classified as plateau high hemoglobin group. A total of 13 male blood donors from Tibet Autonomous Region were recruited. And the female blood donors (n=13) with Hb(115~165) g/L and male blood donors (n=12) with Hb(120~185) g/L from Chengdu were classified as control group. Whole blood of 200 mL specification was centrifuged to remove the plasma, and MAP additive solution was added to prepare SRBCs, then SRBCs were divided into four aliquots (50 mL/bag and stored at 4℃. Parameters as blood routine, free Hb and hemolysis rate were measured aseptically at day 1, 14, 21, 35 of storage. And 10 mL SRBCs was used to extract membrane proteins for tyrosine phosphorylation detection of band 3 protein. 【Results】 The RBCs counts(×1012/L), hematocrit(%) and hemoglobin(g/L) of Tibetan high Hb group and control group were 6.76±0.95 vs 4.65±0.52, 63.3±6.8 vs 43.1±4.4 and 214.4±19.8 vs 143.2±16.9 (P<0.01). The erythrocyte deformability test on the day 1, 14, 21, 35 of storage showed that the deformability of SRBCs prepared from Tibetan high Hb group was significantly lower than that of the control group under shear stress of 3, 5.33, 9.49, 16.87, and 30 Pa, while the hemolysis rate of SRBCs prepared from the Tibetan high Hb group and the control group on the day 1, 14, 21, 35 were 0.050 2±0.040 2 vs 0.022 2±0.011 1, 0.055 4±0.043 vs 0.032 1±0.028 7, 0.061 2±0.025 9 vs 0.034 3±0.031 7 and 0.069 6±0.032 0 vs 0.044 0±0.033 3 (P<0.05). Western blotting showed that the cytoplasmic N-terminal Y21 of band 3 protein of SRBCs prepared from Tibetan high Hb group was highly phosphorylated. 【Conclusion】 The deformability of SRBCs prepared from the Tibetan high Hb group was significantly lower while the hemolysis rate of SRBCs was higher than that of the control group. The hemolysis rate of the SRBCs at the end of storage prepared from the Tibetan high Hb group meets the requirements of the national standard GB18469-2012(<0.8%). The increase of hemolysis rate of SRBCs prepared from the Tibetan high Hb group was closely related to the phosphorylation of band 3 protein.

Utility of a modified vascular corrosion casting technique in the diagnosis of fetal total anomalous pulmonary venous connection.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital cardiac malformation, and prenatal detection of TAPVC malformation remains a challenging. TAPVC can be easily missed or misdiagnosed in prenatal examinations. This study was aimed to use the modified vascular corrosion casting technique to prepare fetal cardiovascular casts with TAPVC and investigate the utility of cardiovascular casting for the demonstration of fetal TAPVC. The retrospective study enrolled twenty fetuses (22 to 29 + 4 gestational weeks) with TAPVC diagnosed by prenatal echocardiography and casting technique from May 2015 to May 2020. Pre- and postnatal medical records, including results obtained by prenatal ultrasound, postpartum computed tomography angiography, as well as anatomic and cardiovascular casting findings were carefully reviewed and analyzed. In twenty cases, 80% (16/20) had intra- or extracardiac malformations. The TAPVC types were supracardiac (n = 8), cardiac (n = 6), infracardiac (n = 4), and mixed (n = 2). The diagnosis of 1 case each of supracardiac and cardiac TAPVC was modified to partial anomalous pulmonary venous connection; additionally, 4 malformations were missed and 2 were misdiagnosed, including an anomalous left brachiocephalic vein in supracardiac TAPVC, abnormal inflow of the hepatic vein and a double inferior vena cava in infracardiac TAPVC; and bilateral ductus arteriosus in infracardiac TAPVC; a tetralogy of Fallot in cardiac TAPVC that was corrected to right ventricular double outlet; and an absence of ductus arteriosus that was misdiagnosed as slim ductus arteriosus. Comparing with ultrasound, casting technique has its own superiority in exhibiting TAPVC abnormalities, especially in certain types such as course, origin and absence abnormalities of ductus. Postpartum cardiovascular casts can accurately depict the branch structure of the heart's larger vessels, and may be used as a clinical assessment and teaching method in complex cardiac malformations.

Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Widespread myocardial dysfunction in COVID-19 patients detected by myocardial strain imaging using 2-D speckle-tracking echocardiography.

COVID-19 is a multiorgan systemic inflammatory disease caused by SARS-CoV-2 virus. Patients with COVID-19 often exhibit cardiac dysfunction and myocardial injury, but imaging evidence is lacking. In the study we detected and evaluated the severity of myocardial dysfunction in COVID-19 patient population using two-dimensional speckle-tracking echocardiography (2-D STE). A total of 218 consecutive patients with confirmed diagnosis of COVID-19 who had no underlying cardiovascular diseases were enrolled and underwent transthoracic echocardiography. This study cohort included 52 (23.8%) critically ill and 166 noncritically ill patients. Global longitudinal strains (GLSs) and layer-specific longitudinal strains (LSLSs) were obtained using 2-D STE. Changes in GLS were correlated with the clinical parameters. We showed that GLS was reduced (<-21.0%) in about 83% of the patients. GLS reduction was more common in critically sick patients (98% vs. 78.3%, P < 0.001), and the mean GLS was significantly lower in the critically sick patients than those noncritical (-13.7% ± 3.4% vs. -17.4% ± 3.2%, P < 0.001). The alteration of GLS was more prominent in the subepicardium than in the subendocardium (P < 0.001). GLS was correlated to mean serum pulse oxygen saturation (SpO2, RR = 0.42, P < 0.0001), high-sensitive C-reactive protein (hsCRP, R = -0.20, P = 0.006) and inflammatory cytokines, particularly IL-6 (R = -0.21, P = 0.003). In conclusions, our results demonstrate that myocardial dysfunction is common in COVID-19 patients, particularly those who are critically sick. Changes in indices of myocardial strain were associated with indices of inflammatory markers and hypoxia, suggesting partly secondary nature of myocardial dysfunction.

Assessing Hemocompatibility of Transfusion Sets for Single Use / 中国输血杂志

【Objective】 To investigate the blood compatibility of transfusion sets for single use, the loss, damage and activation of blood components after passage through the transfusion sets. 【Methods】 Transfusion sets (sample A and B) were assessed by comparing samples of blood component taken prior to and after passage through. The following makers of damage/activation were evaluated: Red blood cells (RBCs)-supernatant free hemoglobin (FHb) and potassium(K+ ) amount; platelet concentrates (PCs)-pH, hypotonic shock response (HSR), supernatant lactate dehydrogenase(LDH), CD62P; fresh frozen plasma(FFP) – prothrombin fragments 1 and 2 (F1+ 2), fibrinopeptide A (FPA), coagulation factor Ⅻa (FⅫa), Thrombin-antithrombin complex (TAT). 【Results】 After passing through two types of transfusion sets, the loss of RBCs, PCs and FFP were less than 5%. There is no statistic difference for the change of FHb and K+ of RBCs(P>0.05). There were no statistics for pH, LDH(U/L) and CD62P(%) after platelet concentrates passing through both transfusion sets. There was no statistics for the HSR after passing through the sample A, while there was a small but statistically significant increase in the HSR of sample B (37.17±6.49 vs 40.75±6.24, P<0.05). After FFP passing through the transfusion giving sets, there were no statistical difference for F1+ 2, FPA, FⅫa and TAT (P>0.05). 【Conclusion】 Two types of transfusion sets caused negligible effects on RBCs, platelet concentrates and FFP.

Analysis of plasma coagulation function in male Tibetan population with different hemoglobin content in Tibet / 中国输血杂志

【Objective】 To explore the correlation between blood coagulation function and hemoglobin(Hb) content in male Tibetan population in Tibet by analyzing and comparing the indexes of blood coagulation function in male Tibetan population with different Hb contents, so as to provide the basis for formulating blood donation criteria and blood component quality standard suitable for high altitude area. 【Methods】 Male Tibetans in Tibet during November 2018 to January 2019 were randomly selected and divided into three groups according to the Hb content. The healthy male volunteers in plain area were taken as the control. The plasma PT, APTT, TT, Fg, coagulation factor Ⅱ(FⅡ), FⅤ, FⅦ, FⅧ, FⅨ, FⅩ, FⅪ, FⅫ and protein C(PC) content of each group were measured and compared. 【Results】 The Fg was not different by groups(P>0.05); PT, APTT and TT in group C (Hb>210 g/L) in Tibet were significantly higher than those in controls [PT( s) : 11.48±1.18 vs 13.79±3.73; APTT( s) : 36.71±2.93 vs 43.30±4.56; TT( s) : 15.77±0.95 vs 17.94±2.43, P0.05), except PC conctent of group A was slightly higher than that of group B. 【Conclusion】 The plasma characteristics of Tibetan male with Hb content more than 210 g/L is different from that in plain and other high altitude area, such as prolonged coagulation time and significantly decreased coagulation factor content. Therefore, it is important to put forward the health examination requirements for blood donors and quality standards for whole blood and blood components suitable for high altitude areas in Tibet.

Utility of modified vascular corrosion casting technique in the diagnosis of fetal ductus arteriosus abnormalities.

The anatomy of ductus arteriosus (DA) can be varied in different congenital heart defects (CHDs), and it is difficult to fully discover the DA and other associated cardiac anomalies by prenatal ultrasound. This study was aimed to use the modified vascular corrosion casting technique to prepare fetal cardiovascular casts with DA anomalies, assess the casting effectiveness in evaluating the great vessels of the fetal heart and investigate the utility of cardiovascular casting for the demonstration of fetal DA abnormalities. This retrospective study enrolled fourteen fetuses (23 to 28+2 gestational weeks) with severe CHDs diagnosed by prenatal echocardiography and casting technique from January 2013 to July 2019. The sonographic features of DAs were carefully observed and other associated cardiovascular anomalies were also evaluated during the screening. The architectures of DAs and the whole cardiovascular system were observed and analyzed, and then the cast findings were compared with prenatal ultrasonic results. In fourteen cases, 18 ductal abnormities were indicated by prenatal echocardiography in fourteen cases, while 25 were revealed by casting. Cast findings included 4 cases of ductal stenosis, 1 case of ductal dilation, 6 cases of ductal circuity, 3 cases of right-sided ductus, 5 cases of anomalous ductal connection, 1 case of bilateral ductus and 5 cases of absent ductus. Cast findings consisted with ultrasound in 10 ductal abnormalities, revealed additional 15 ductal abnormalities miss-diagnosed by sonography, and corrected 6 abnormalities misdiagnosed prenatally. Meanwhile, 3 ductal abnormalities (reversed flow) could not be demonstrated by casts but only by ultrasound. Cast models can visually display the anatomical characteristics of ductus arteriosus, and could be successfully used in the demonstration of ductus abnormalities in fetuses with severe CHDs. Comparing with ultrasound, casting technique has its own superiority in exhibiting ductus abnormalities, especially in certain types such as course, origin and absence abnormalities of ductus.

Description of misdiagnosis and missed diagnosis of fetal complex heart malformations by prenatal echocardiography combined with postnatal cardiovascular casting.

OBJECTIVE: To compare prenatal echocardiography with postnatal cardiovascular casting for detection of fetal cardiovascular malformations, and to discuss the causes of prenatal misdiagnosis and missed diagnosis. METHODS: We retrospectively identified patients from 2013 to 2018 at our Maternal-Fetal Medicine Center who were reported to have a fetal diagnosis of severe congenital heart malformations (CHMs). Subjects had postnatal confirmation of CHMs. Prenatal and postnatal medical records, including ultrasound results and casting findings, were reviewed and analyzed. RESULTS: Postnatal casting showed that all 35 fetuses had complex CHMs. In these 35 cases, 90 cardiovascular malformations were found by postnatal casting, and 69 were detected by prenatal echocardiography. Among the other 21 cardiovascular malformations, 7 were misdiagnosed and 14 diagnoses were missed by prenatal ultrasound. CONCLUSION: Prenatal echocardiography may lead to misdiagnosis and missed diagnoses, especially in cases with great arterial branching anomalies. Postnatal casting can demonstrate the configuration of the great vessels and smaller branches directly. Thus, understanding of such malformations via postnatal casting may help to improve prenatal diagnostic accuracy.

Combining antioxidant astaxantin and cholinesterase inhibitor huperzine A boosts neuroprotection.

Oxidative stress is a pathophysiological condition resulting in neurotoxicity, which is possibly associated with neurodegenerative disorders. In this study, the antioxidative effects of the antioxidant astaxanthin (AXT) in combination with huperzine A (HupA), which is used as a cholinesterase inhibitor for the treatment of Alzheimer's disease, were investigated. PC12 cells were treated with either tert­butyl hydroperoxide (TBHP), or with the toxic version of ß­amyloid, Aß25­35, to induce oxidative stress and neurotoxicity. Cell viability, morphology, lactate dehydrogenase (LDH) release, intracellular accumulation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined, while neuroprotection was also monitored using an MTT assay. It was found that combining AXT with HupA significantly increased the viability of PC12 cells, prevented membrane damage (as measured by LDH release), attenuated intracellular ROS formation, increased SOD activity and decreased the level of MDA after TBHP exposure when compared to these drugs administered alone. Pretreatment with HupA and AXT decreased toxic damage produced by Aß25­35. These data indicated that combining an antioxidant with a cholinesterase inhibitor increases the degree of neuroprotection; with future investigation this could be a potential therapy used to decrease neurotoxicity in the brain.

Key Role of CD151-integrin Complex in Lung Cancer Metastasis and Mechanisms Involved.

Tetraspanin CD151 was found to be upregulated in malignant cell types and has been identified as a tumor metastasis promoter. In this study, we aimed to examine the role of the CD151-integrin complex in lung cancer metastasis and the underlying mechanisms. CD151 QRD194-196 →AAA194-196 mutant was generated and used to transfect A549 human lung adenocarcinoma cells. We found that there was no significant difference in CD151 protein expression between CD151 and CD151-AAA mutant groups. In vitro, CD151-AAA mutant delivery abrogated the migration and invasion of A549 cells, which was promoted by CD151 gene transfer. Furthermore, CD151-AAA delivery failed to activate FAK and p130Cas signaling pathways. Western blot and immunohistochemical staining showed strong CD151 expression in lung cancerous tissues but not in adjacent normal tissues. Increased level of CD151 protein was observed in 20 of the patients and the positive rate of CD151 protein in specimens was 62.5% (20/32). In addition, CD151 was co-localized with α3 integrin at the cell-cell contact site in carcinoma tissues. These results suggested that the disruption of the CD151-α3 integrin complex may impair the metastasis-promoting effects and signaling events induced by CD151 in lung cancer. Our findings identified a key role for CD151-α3 integrin complex as a promoter in the lung cancer.

Congenital Cystic Adenomatoid Malformation Volume Ratio in Prenatal Assessment of Prognosis of Fetal Pulmonary Sequestrations.

This study aimed to evaluate the prognosis of pulmonary sequestration (PS) by measuring congenital cystic adenomatoid malformation volume ratio (CVR) value in fetal congenital PS. The fetal CVR in 49 cases of fetal PS diagnosed by prenatal ultrasound in Xiangyang No. 1 People's Hospital from March 2010 to June 2017 were measured, and the clinical outcomes were observed. According to the prenatal ultrasound CVR value, 49 fetuses diagnosed with PS were divided into 2 groups: group 1 with CVR≥1.26, and group 2 with CVR<1.26. The incidence rate of fetal edema, respiratory distress symptoms and survival rate were compared between the two groups. The risk factors of the fetal PS were evaluated by single and multiple Logistic regression analysis. The correlation between CVR and fetal prognosis was analyzed. Of the 49 fetuses, there were 34 cases of PS (ILS) type (69.39%, 34/49), 10 cases of PS (ELS) type I (20.41%, 10/49) and 5 cases of PS (ELS) type II (10.20%, 5/49). Forty-six cases (93.88%, 46/49) were born alive, there was 1 case (CVR ≥1.26) (2.04%, 1/49) of induced abortion, and 2 cases (CVR ≥1.26) (4.08%, 2/49) of stillbirths. In group 1 (n=24), 21 cases were born alive, and the incidence rate of newborn respiratory distress and fetal edema was 100% (21/21) and 79.17% (19/24) respectively. In group 2 (n=25), there were 3 cases (12%,3/25) of newborn respiratory distress, 3 cases (12%, 3/25) of fetal edema, and the rate of live birth was 100%. There were statistically significant differences between the two groups in the incidence of fetal edema, postpartum respiratory symptoms and survival rate. CVR was a risk factor for PS and was associated with fetal prognosis. CVR in the midtrimester of pregnancy is an effective index to evaluate the prognosis of fetal PS. CVR ≥1.26 is associated with an increased risk of fetal edema, infant respiratory distress and intrauterine or postnatal death.

Global Longitudinal Strain at Rest for Detection of Coronary Artery Disease in Patients without Diabetes Mellitus.

Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD). However, the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown. In the present study, 211 patients with suspected CAD were prospectively included, with DM patients excluded. All patients underwent echocardiography and subsequently coronary angiography within 3 days. Left ventricular (LV) GLSs were quantified by 2D STE. Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model. Critical CAD was defined as an area stenosis ≥70% in ≥1 epicardial coronary artery (≥50% in left main coronary artery). Totally 145 patients were diagnosed as having critical CAD by coronary angiography. Significant differences were observed in all strain parameters between patients with and without critical CAD. The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of -19.05% with sensitivity of 78.1% and specificity of 72.7%, which increased to 0.926 after exclusion of apical segments (cut-off value -18.66%; sensitivity 84.4% and specificity 81.8%). The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries. The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery, left anterior descending (LAD) artery and right coronary artery (RCA), in order of diagnostic accuracy, was 0.818 for LCX, 0.764 for LAD and 0.723 for RCA, respectively. In conclusion, in non-DM patients with suspected CAD, GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy, and a higher cut-off point than reported before should be used. Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS. It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.

Highly extended filaments in aqueous gold nano-particle colloidals.

A new regime of filamentation has been discovered in aqueous gold nanoparticle colloidals (AGNC). Different from filamentation in liquids, in this regime, by doping water with gold nanoparticles, there is no observable multiple small-scale filaments, but instead a spatially continuous plasma channel is formed. The length of the filament is more than ten times as compared with that in water. Filamentation in AGNC is characterized by a colorful light channel, with generated supercontinuum ranging from 400 nm to 650 nm which is scattered along a cyan-orange path.

Treatment effects of systematic two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: rationale and design of a prospective, randomised and multicentre DEFINITION II trial.

INTRODUCTION: Provisional stenting (PS) for simple coronary bifurcation lesions is the mainstay of treatment. A systematic two-stent approach is widely used for complex bifurcation lesions (CBLs). However, a randomised comparison of PS and two-stent techniques for CBLs has never been studied. Accordingly, the present study is designed to elucidate the benefits of two-stent treatment over PS in patients with CBLs. METHODS AND ANALYSIS: This DEFINITION II study is a prospective, multinational, randomised, endpoint-driven trial to compare the benefits of the two-stent technique with PS for CBLs. A total of 660 patients with CBLs will be randomised in a 1:1 fashion to receive either PS or the two-stent technique. The primary endpoint is the rate of 12-month target lesion failure defined as the composite of cardiac death, target vessel myocardial infarction (MI) and clinically driven target lesion revascularisation. The major secondary endpoints include all causes of death, MI, target vessel revascularisation, in-stent restenosis, stroke and each individual component of the primary endpoints. The safety endpoint is the occurrence of definite or probable stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been approved by the Institutional Review Board of Nanjing First Hospital, and accepted by each participating centre. Written informed consent was obtained from all enrolled patients. Findings of the study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT02284750; Pre-results.