Efficacy on the Acute Lumen Gain Post Excimer Laser Combined With Drug-coated Balloon for Instent Restenosis and the Relationship With Different Neointimal Tissues Defined by Optical Coherence Tomography / 中国循环杂志

Objectives:To compare the efficacy of the combination of excimer laser coronary angioplasty(ELCA)and drug-coated balloon(DCB)for in-stent restenosis(ISR)and to evaluate the impact of neointimal tissue characteristics on treatment outcomes. Methods:A total of 96 ISR lesions from 86 patients who underwent optical coherence tomography(OCT)evaluation and DCB with or without ELCA treatment at The First Medical Center of Chinese PLA General Hospital from January 2019 to May 2023 were retrospectively analyzed.ISR lesions were divided into ELCA+DCB group(n=30)and DCB group(n=66).Additionally,ISR lesions were classified as homogeneous and non-heterogeneous patterns based on the OCT characteristics of the neointimal tissue,and the impact on acute lumen gains was compared between different ISR patterns.Acute lumen gain(ΔMLA)was defined as the changes in minimum lumen area before and after the intervention. Results:The ELCA+DCB group had a significantly greater ΔMLA than the DCB group([3.2±0.8]mm2 vs.[2.6±1.4]mm2,P=0.015).Among the ISR with a homogeneous pattern,the ΔMLA of the ELCA+DCB group was significantly greater than that of the DCB group([3.0±0.9]mm2 vs.[2.2±1.1]mm2,P=0.030).There was no significant difference in ΔMLA between the two ISR groups with the non-homogeneous pattern([3.4±0.7]mm2 vs.[3.2±1.5]mm2,P=0.533).There was no death,the rate of target lesion revascularization was similar between the patients with lesions receiving DCB treatment and patients receiving ELCA +DCB treatment(7.4%vs.4.2%,P＞0.05). Conclusions:The combination of ELCA and DCB is an effective strategy for treating ISR,which can achieve greater acute lumen gain compared to DCB treatment alone,especially for the treatment of homogenous ISR pattern characterized by OCT.

Clustering analysis of risk factors in high-incidence areas of esophageal cancer in Yanting county / 中国胸心血管外科临床杂志

@#Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Predictive value of non-enhanced CT combined with clinical indicators in severe acute pancreatitis / 中华急诊医学杂志

Objective:To establish and validate a nomogram model for early prediction of the risk of acute pancreatitis (AP) progressing to severe acute pancreatitis (SAP).Methods:CT signs and clinical laboratory parameters of 361 AP patients admitted to our Hospital from January 2016 to July 2022 were retrospectively collected. There were 221 males (61.2%) and 140 females (38.8%). According to the Atlantic score, all patients were divided into the SAP group (64 cases) and the non-SAP (NSAP) group (297 cases). Univariate analysis was used to screen out variables with statistically significant differences. Multivariate Logistic regression analysis was used to screen out the independent risk factors of SAP, and finally a nomogram prediction model was established. Receiver operating characteristic (ROC) curve, calibration curve and decision curve (DCA) were used to evaluate the predictive efficacy, accuracy and clinical practicability of the model, and Bootstrap method was used to verify the model internally.Results:Univariate analysis and multivariate Logistic regression analysis showed that pleural effusion ( OR=7.353, 95% CI: 3.344-16.170), posterior pararenal space (PPS) involvement ( OR=3.149, 95% CI: 1.314-7.527), serum creatinine concentration (Cr) ( OR=1.027, 95% CI: 1.017-1.038) and serum calcium concentration (Ca 2+) ( OR=0.038, 95% CI: 0.009-0.166) were independent risk factors for SAP ( P<0.05). A Nomogram model was established based on these four factors. The area under the ROC curve (AUC) of this model was 0.905 (95% CI: 0.869-0.933), indicating high predictive efficiency. Internal verification showed that the model had good accuracy in predicting SAP, and C-index was 0.90. DCA analysis showed that the model had high clinical practicability. Conclusions:The Nomogram model combining pleural effusion, PPS involvement, Cr and Ca 2+ had a good effect on early prediction of SAP, which could provide a new reference tool for clinical diagnosis and treatment.

Optimizing the risk stratification of coronary CT angiography for non-obstructive coronary artery disease based on cluster analysis / 中华放射学杂志

Objective:To explore the risk stratification value of coronary CT angiography (CCTA) in patients with non-obstructive coronary artery disease based on cluster analysis and to identify the high-risk population of cardiovascular adverse events in patients.Methods:Prospective consecutive patients with suspected coronary artery disease who underwent CCTA examination and were confirmed as non-obstructive coronary heart disease were enrolled in the General Hospital of Chinese PLA from January 1, 2015 to December 31, 2017. The clinical characteristics and CCTA diagnosis information of patients were collected, and then follow-up was performed to obtain adverse cardiovascular events. Firstly, the cluster analysis based on CCTA information divided the patients into different groups. Then, the risk of adverse cardiovascular events was compared between different groups. Finally, segment involvement score (SIS) score, Leiden score, SIS score combined with clinical characteristics, Leiden score combined with clinical characteristics, and cluster information combined with clinical characteristics were used to stratify the population, and the concordance index-time curve and net reclassification improvement (NRI) index were described to compare the risk stratification ability of the five different models.Results:A total of 3 402 patients with non-obstructive coronary artery disease were included in the study, of whom 104 had adverse cardiovascular events during the follow-up period. Cluster analysis based on CCTA information classified patients into 3 different groups. There were statistically significant differences in clinical characteristics, CCTA information, and survival outcomes between groups ( P<0.05). The results of the concordance index-time curve showed that the risk stratification ability of CCTA cluster information combined with clinical characteristics was better than the current SIS score, Leiden score, SIS score combined with clinical characteristics, Leiden score combined with clinical characteristics. At the 1-year and 2-year time cutoffs, cluster information combined with clinical characteristics showed a positive increase in INR compared with the first four models (INR was 0.248 and 0.293, 0.316 and 0.293, 0.147 and 0.003, 0.192 and 0.007, respectively). Conclusion:CCTA based on cluster analysis has a good risk stratification value for patients with non-obstructive coronary artery disease and is helpful for individualized intervention.

Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma / 医学前沿

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

Discovery of novel aporphine alkaloid derivative as potent TLR2 antagonist reversing macrophage polarization and neutrophil infiltration against acute inflammation

Toll-like receptor 2 (TLR2) mediated macrophages regulate the protective immune response to infectious microorganisms, but the aberrant activation of macrophages often leads to pathological inflammation, including tissue damage. In this study, we identified antagonists of TLR2 by screening 2100 natural products and subsequently identified Taspine, an aporphine alkaloid, as an excellent candidate. Furthermore, analysis of the 10 steps chemical synthesis route and structural optimization yielded the Taspine derivative SMU-Y6, which has higher activity, better solubility, and improved drug-feasible property. Mechanistic studies and seq-RNA analysis revealed that SMU-Y6 inhibited TLR2 over other TLRs, hindered the formation of TLR2/MyD88 complex, and blocked the downstream NF-κB and MAPK signaling pathway, thus suppressing the release of inflammatory cytokines. SMU-Y6 could stabilize TLR2 and bind to TLR2 protein with a Kd of 0.18 μmol/L. Additionally, SMU-Y6 could efficiently reverse the M1 phenotype macrophage polarization, reduce the production of cytokines as well as infiltration of neutrophiles and alleviate the local inflammation in mice with acute paw edema and colitis. Collectively, we reported the first aporphine alkaloid derivative that selectively inhibits TLR2 with high binding affinity and superior drug-feasible property, thus providing an urgently-needed molecular probe and potential drug candidate for inflammatory and autoimmune disease therapy.

A pretest model of obstructive coronary artery disease based on machine learning: from the C-Strat study / 中华内科杂志

Objective:To develop a pretest probability model of obstructive coronary artery disease with machine learning based on multi-site Chinese population data.Methods:Chinese regiStry in early deTection and Risk strAtificaTion of coronary plaques (C-Strat) study is a prospective multi-center cohort study, in which consecutive patients with suspected obstructive coronary artery disease and ≥64 detector row coronary computed tomography angioplasty (CCTA) evaluation were included. Data from the patients were randomly split into a training set (70%) and a test set (30%). More than 50% of coronary artery stenosis by CCTA was defined as positive outcome. A boosted ensemble algorithm (XGBoost), 10-fold cross-validation and Bayesian optimization were used to establish a new prediction model-CARDIACS(pretest probability model from Chinese registry in eARly Detection and rIsk stratificAtion of Coronary plaques Study), and a logistic regression was used to establish a model-LOGISTIC in training set. The test set was used for validation and comparison among CARDIACS, LOGISTIC, UDFM (updated Diamond-Forrester Model) and DFCASS(Diamond-Forrester and CASS).Results:The study population included 29 455 patients with age of (57.0±9.7) years and 44.8% women, of whom 19.1% (5 622/29 455) had obstructive coronary artery disease. For CARDIACS, the age, the reason for visit and the body mass index (BMI) were the most important predictive variables. In the independent test set, the area under the curve (AUC) of CARDIACS was 0.72 (95% CI 0.70-0.73), which was significantly superior to that of LOGISTIC (AUC 0.69, 95% CI 0.68-0.71, P=0.015), UDFM (AUC 0.64, 95% CI 0.62-0.65, P<0.001) and DFCASS (AUC 0.66, 95% CI 0.64-0.67, P<0.001), respectively. Conclusion:Based on Chinese population, the study developed a new pretest probability model--CARDIACS, which was superior to the traditional models. CARDIACS is expected to assist in the clinical decision-making for patients with stable chest pain.

A modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane (with video demonstration) / 器官移植

Objective To modify the mouse model of orthotopic left lung transplantation from different perspectives, aiming to establish a simpler, faster and stabler mouse model of lung transplantation. Methods Based on preliminary modified rat model of orthotopic left lung transplantation established by our team, varying extent of modifications were made regarding the tracheal intubation, cannula preparation and anastomosis procedures of orthotopic left lung transplantation in the recipient mice. Orthotopic left lung transplantation in 40 mice were performed by an operator with microsurgical experience. The dissection of the recipient's hilar structure was carried out at the plane of the hilar clamp model within the reverse-view, and the three branches (left main bronchus, pulmonary artery and pulmonary vein) of the pulmonary hilum were anastomosed in turn by the "pendulum" anastomosis method. The operation time of each procedure was recorded. The recipient mice were sacrificed at postoperative 2 weeks, and the incidence of postoperative complications was recorded. Results Lung transplantation was successfully completed in 40 mice, with no bronchial and vascular tearing or twisting, and no bleeding at the anastomosis site. The overall cardiopulmonary procurement time was (10.7±1.5) min, cannula preparation time was (16.2±1.5) min, cold ischemia time was (25.1±2.4) min, warm ischemia time was (19.4±1.6) min, and the total operation time was (57.2±2.9) min, respectively. During the follow-up from 6 to 14 days after surgery, one recipient mouse died of pleural effusion, probably caused by infection. No pneumothorax, thrombosis or atelectasis was found in the remaining recipient mice during postoperative follow-up. Conclusions The modified mouse model of orthotopic left lung transplantation based on "pendulum" anastomosis of the reverse-view plane possesses multiple advantages of short operation time, high success rate and few complications, which is expected to become an alternative model of studying pathological changes after lung transplantation and worthy of further application.

Proteomic biomarkers of depression / 四川精神卫生

This study aims to review the biomarkers of depression discovered by proteomic techniques to guide the identification of specific biomarkers for depression. Depression is a common psychological disease， and its diagnosis and efficacy evaluation rely on subjective clinical evaluation， lacking objective diagnostic tools. Proteomics is the primary method to discover and verify biomarkers. This study reviews proteomic biomarkers in brain tissue， cerebrospinal fluid and blood of patients with depression， as well as the latest strategies for screening biomarkers of depression.

Association between myostatin and sarcopenia in end-stage liver disease / 临床肝胆病杂志

Patients with end-stage liver disease (ESLD) are often accompanied by various complications such as sarcopenia and cachexia including lipopenia, and it was believed in the past that such status was associated with malnutrition, while recent studies have shown that myostatin (MSTN) is associated with the progression of ESLD. MSTN can lead to sarcopenia and cachexia by affecting the metabolism of glucose, fat, and protein and the number of myocytes, and it can be used as a screening indicator for hepatocellular carcinoma (HCC) and an indicator for disease progression. Intervention via the MSTN pathway might be an effective method for controlling sarcopenia and cachexia in patients with ESLD, and MSTN may be an effective indicator for predicting the progression of liver cirrhosis to HCC.

Modulatory Potential of LncRNA Zfas1for Inflammation and Neuronal Apoptosis in Temporal Lobe Epilepsy

Purpose@#This study aimed to elucidate whether lncRNA ZFAS1 is involved in neuronal apoptosis and inflammation in temporal lobe epilepsy (TLE). @*Materials and Methods@#Ninety-six TLE patients were recruited, and their peripheral venous blood was gathered to determine Zfas1 expression with polymerase chain reaction. Neurons were separated from hippocampal tissue of newborn SD rats, and siZfas1 or pcDNA3.1-Zfas1 was transfected into the neurons. Inflammatory cytokines released by neurons were determined, and neuronal activities were evaluated through MTT assay, colony formation assay, and flow cytometry. @*Results@#Serum levels of Zfas1 were higher in TLE patients than in healthy controls (p<0.05). Furthermore, Zfas1 expression in neurons was raised by pcDNA3.1-Zfas1 and declined after silencing of Zfas1 (p<0.05). Transfection of pcDNA-Zfas1 weakened the viability and proliferation of neurons and increased neuronal apoptosis (p<0.05). Meanwhile, pcDNA3.1-Zfas1 transfection promoted lipopolysaccharide-induced release of cytokines, including tumor necrosis factor-α, interleukin (IL)-1, IL-6, and intercellular adhesion molecule-1 (p<0.05), and boosted NF-κB activation by elevating the expression of NF-κB p65, pIκBα, and IKKβ in neurons (p<0.05). @*Conclusion@#Our results indicated that lncRNA ZFAS1 exacerbates epilepsy development by promoting neuronal apoptosis and inflammation, implying ZFAS1 as a promising treatment target for epilepsy.

Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route

The authors have withdrawn this manuscript (Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route) from medRxiv, because it was found that the statistical and analytical methods used in the manuscript had certain controversies after further discussion, so the authors of the manuscipt disclaimed that this conclusion cannot be used as the basis for the origin and evolution of SARS-COV-2, also as information to guide clinical practice and health-related behaviors, it should not be reported as established facts in the news media and "We-Media". No one should do too much extended interpretation of the content of this manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Immunotherapy for treating methamphetamine, heroin and cocaine use disorders.

Drug addiction is a serious health problem prevalent worldwide. Currently available therapies including pharmacotherapy and psychotherapy are insufficient to meet the clinical needs for treating drug abuse. Recently, immunotherapy has emerged as a promising approach to treat such drug-use disorders. Pharmacokinetic antagonists are used in immunotherapy, functioning by sequestering the drugs in the periphery but without allowing the drug to cross the blood-brain barrier. This can reduce the toxic and rewarding effects of the drugs, while preventing addiction and facilitating reduced relapse rates. Herein, we update recent developments in the immunotherapeutic strategies to treat abuse of drugs like methamphetamine, heroin and cocaine. In addition, we summarize the drug design used so far and its optimization strategies. Further, we document the efficacy of anti-drug vaccines and monoclonal antibodies, with an aim to promote development of new anti-drug immunotherapies.

Animal experimental study of endoscopic cholecystolithotomy after lumen-apposing metal stent implantation (with video) / 中华消化内镜杂志

Objective:To investigate the safety and feasibility of endoscopic cholecystolithotomy after endoscopic ultrasonography (EUS)-guided lumen-apposing metal stent (LAMS) implantation in animals.Methods:Six miniature pigs of 30-35 kg were selected to laparotomy under intravenous anesthesia. Two to four sterile human stones with diameter of 0.8-2.0 cm were implanted in their gallbladder. After successful modeling, LAMS was implanted between the stomach and gallbladder under the guidance of EUS. Ultrafine endoscope was used to search and remove stones after passing the gastric stent into the gallbladder. Endoscopic sphincterotomy (EST) and endoscopic retrograde biliary drainage (ERBD) was performed to prevent bile leakage. And then ordinary endoscope was used to remove LAMS and close the wound. The success rate, operation time, and incidence of complications were analyzed.Results:Five pigs were successfully implanted with LAMS, and the ultrafine endoscope entered the gallbladder smoothly. Small stones were removed from the stone basket, and large stones were completely removed after laser lithotripsy. The total operation time was 87-128 min. No postoperative complications such as bleeding, perforation, infection, or biliary fistula were observed. Failure in 1 pig was due to the first EST plus ERBD, resulting in rapid reduction of gallbladder volume and away from the gastric cavity leading to puncture difficulties.Conclusion:Endoscopic cholecystolithotomy after EUS-guided LAMS implantation is safe and feasible, and may provide animal experimental evidence for potential therapeutic approach for patients with difficulty in cholecystectomy.

Biopsy of pulmonary nodules guided by different imaging techniques / 肿瘤研究与临床

Lung cancer is a highly malignant tumor with poor prognosis.For advanced lung cancer patients,a wide range of invasion,multiple distant metastases and the limited treatment options have led to extremely poor prognosis.Better treatment outcome with a high 5-year survival rate can be achieved by early detection and treatment of lung cancer.The early diagnosis is the key to the treatment of lung cancer,and the early diagnosis of lung cancer depends on the identification of benign and malignant of pulmonary nodules.With the increased safety and diagnostic accuracy of biopsy of pulmonary nodules guided by different imaging techniques,the advantage of biopsy of pulmonary nodules in diagnosis of benign and malignant lesions is prominent,which is worthy of clinical application.

Correlation of Gut Microbiome Between ASD Children and Mothers and Potential Biomarkers for Risk Assessment / 基因组蛋白质组与生物信息学报·英文版

Variation of maternal gut microbiota may increase the risk of autism spectrum disorders (ASDs) in offspring. Animal studies have indicated that maternal gut microbiota is related to neurodevelopmental abnormalities in mouse offspring, while it is unclear whether there is a correlation between gut microbiota of ASD children and their mothers. We examined the relationships between gut microbiome profiles of ASD children and those of their mothers, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. Gut microbiome was profiled and evaluated by 16S ribosomal RNA gene sequencing in stool samples of 59 mother-child pairs of ASD children and 30 matched mother-child pairs of healthy children. Significant differences were observed in the gut microbiome composition between ASD and healthy children in our Chinese cohort. Several unique bacterial biomarkers, such as Alcaligenaceae and Acinetobacter, were identified. Mothers of ASD children had more Proteobacteria, Alphaproteobacteria, Moraxellaceae, and Acinetobacter than mothers of healthy children. There was a clear correlation between gut microbiome profiles of children and their mothers; however, children with ASD still had unique bacterial biomarkers, such as Alcaligenaceae, Enterobacteriaceae, and Clostridium. Candidate biomarkers discovered in this study had remarkable discriminatory power. The identified patterns of mother-child gut microbiome profiles may be important for assessing risks during the early stage and planning of personalized treatment and prevention of ASD via microbiota modulation.

Non-invasive quantitative plaque analysis by coronary CT angiography in predicting coronary hemodynamic significance / 中华放射学杂志

Objective To evaluate the diagnostic performance of the automated quantitative analysis by coronary computed tomography angiography (CCTA) for lesion specific hemodynamic significance assessed by fractional flow reserve(FFR). Methods One hundred and fifteen patients with one hundred and fifty?one vessels,who successively underwent invasive coronary angiography with evaluation of FFR(values≤0.8 were defined as lesion specific hemodynamically significant), were analyzed by coronary CT angiography. FFR≤0.80 was found in 54(35.76％) of the 151 vessels, which was divided into two groups (group of hemodynamically significant and group of hemodynamically non-significant). CCTA images were quantitatively analyzed with automated software to obtain the following index:minimal lumen diameter(MLD), maximum diameter stenosis(MDS％), minimal lumen area(MLA), maximum area stenosis(MAS％), lesion length (LL), total plaque volume(TPV), total plaque burden(TPB), calcified plaque volume(CPV), calcified plaque burden (CPB), non-calcified plaque volume(NCPV), non-calcified plaque burden(NCPB), lipid plaque volume(LPV), lipid plaque burden(LPB), fibrous plaque volume(FPV), fibrous plaque burden(FPB), napkin-ring sign(NRS), remodeling index(RI) and eccentric index(EI). Logistic regression and area under the receiver operating characteristics were used for statistical analysis. Results MDS％(65.04％± 8.20％), MAS％(73.91％± 7.58％), TPB(57.96％± 11.17％), CPB[4.32％(0.11％, 5.34％)], LPB[14.89％(9.30％, 19.23％)], CPV[30.68 (0.29, 33.36)mm3], LPV[(81.72(33.92, 94.68)mm3]in the group with hemodynamic significance were larger than those in group with normal hemodynamic status[58.27％± 9.50％, 64.83％± 8.31％, 53.88％± 11.77％, 2.05％(0.00％, 3.42％), 11.83％(6.34％, 16.8％), 12.53(0.00, 13.24)mm3, 60.71(24.1, 75.11)mm3, respectively], which was statistically significant(t=4.41,P<0.01;Z=6.63,P<0.01;t=2.08,P<0.05;Z=-2.47,P<0.01;Z=-2.30,P<0.05;Z=-2.48, P<0.01;Z=-2.55, P<0.01, respectively). MLD[1.24(1.04, 1.46)mm]and MLA[3.61(2.40, 4.80) mm2]in the group with hemodynamic significance were smaller than those in group with normal hemodynamic status[1.53(1.32,1.72)mm, 5.28(4.00,6.40)mm2],which was statistically significant[Z=-4.82,-5.40, respectively;P<0.01].In logistic regression analysis, only MAS％(OR:1.08,95％CI:1.01-1.15,P=0.02), CPB (OR:1.16,95％CI:1.02-1.33,P=0.02) and LPB(OR:1.10,95％CI:1.01-1.19,P=0.02), MLA(OR:0.69, 95％CI:0.49-0.98,P=0.04)were significant predictors of hemodynamic significance. For predicting lesion specific hemodynamic significance, compared with MLA(0.76), MDS％(0.71), CPB(0.62) and LPB(0.61), except for MLA(Z=0.77, P=0.44), the AUC of MAS％(0.79) was significantly increased(Z=2.54, P=0.01;Z=2.91, P<0.01;Z=2.94, P<0.01, respectively). However, combination of other index to MAS％[MAS％+MLA％(0.81), MAS％+MDS％(0.80), MAS％+TPB(0.80), MAS％+CPB(0.80), MAS％+LPB(0.81)] did not show significantly difference over MAS％(Z=1.10, 0.71, 0.40, 0.54, 1.07, respectively;P>0.05). Conclusion Compared with diameter stenosis, area stenosis substantially improves the prediction of lesion specific hemodynamic significance.

A pilot study on the noninvasive fluid hemodynamic investigation of coronary plaque / 中华心血管病杂志

Objective@#To characterize the hemodynamic force towards coronary plaque based on noninvasive coronary computed tomographic angiography and to investigate its relationship with plaque features and stenosis severity by computational fluid dynamics.@*Methods@#Twenty-six patients underwent invasive fractional flow reserve measurement following coronary computed tomography angiography examination from March to September 2016 were retrospectively included. Computational fluid dynamics was applied and wall shear stress (WSS) and axial plaque stress (APS), which extracted the axial component of hemodynamic stress acting on stenotic lesions, were calculated based on the results of noninvasive coronary computed tomographic angiography. Plaque analysis was performed to elucidate plaque features and relative plaque burden. The fluid dynamics distributions in lesions with different stenosis severity were investigated.@*Results@#Thirty-one coronary plaques with satisfactory imaging quality were analyzed, there were 11 (35.5%) dominant low WSS (<1 Pa) lesion and 20 high WSS lesion (64.5%), 8(25.8%) net retrograde APS lesion and 23(74.2%) anterograde lesion. Plaque volume was (78.5±48.6) mm3 and plaque burden was (69.1±12.1)% in the low WSS group, which was(60.5±57.3) mm3, and(57.5±14.0)%, respectively in the high WSS group, the plaque burden was significantly higher in the low WSS group than in the high WSS group (P=0.028), while the percentage of calcified plaque, fibrotic plaque and lipid core volume were similar between the two groups (P>0.05). Plaque volume was (79.7±69.1) mm3 and plaque burden was(68.7±13.7)% in the group with anterograde-dominant APS plaque, which was(61.7±24.9)mm3, and(68.9±10.4)%, respectively in the net retrograde APS lesion group (P>0.05). Percentage of lipid core area was significantly higher in the anterograde lesion group than in the retrograde lesion group ((25.1±18.1)% vs.(10.8±12.7)%, P=0.049). Both WSS and APS were significant higher in the severe obstructive coronary stenosis group than in non-severe obstructive coronary stenosis group (P<0.05). Although there was no difference in WSS between functional coronary ischemia group and non-functional coronary ischemia group ( (13.3±8.7) Pa vs. (12.5±14.2) Pa, P>0.05), the distribution of APS was different between the functional coronary ischemia group and non-functional coronary ischemia group ((1 698.8±652.6) Pa vs. (981.4±787.5) Pa, P<0.05).@*Conclusion@#WSS and APS can uniquely characterize the stenotic segment and has a strong relationship with lesion geometry. APS may be related to the necrotic core plaque and functional coronary ischemia. Clinical application of these hemodynamic and geometric indices may be helpful to assess the future risk of plaque progress and plaque rupture, which will be helpful on determining respective treatment strategy for patients with coronary artery disease.

Characteristics Detected on Computed Tomography Angiography Predict Coronary Artery Plaque Progression in Non-Culprit Lesions

OBJECTIVE: This study sought to determine whether variables detected on coronary computed tomography angiography (CCTA) would predict plaque progression in non-culprit lesions (NCL). MATERIALS AND METHODS: In this single-center trial, we analyzed 103 consecutive patients who were undergoing CCTA and percutaneous coronary intervention (PCI) for culprit lesions. Follow-up CCTA was scheduled 12 months after the PCI, and all patients were followed for 3 years after their second CCTA examination. High-risk plaque features and epicardial adipose tissue (EAT) volume were assessed by CCTA. Each NCL stenosis grade was compared visually between two CCTA scans to detect plaque progression, and patients were stratified into two groups based on this. Logistic regression analysis was used to evaluate the factors that were independently associated with plaque progression in NCLs. Time-to-event curves were compared using the log-rank statistic. RESULTS: Overall, 34 of 103 patients exhibited NCL plaque progression (33%). Logistic regression analyses showed that the NCL progression was associated with a history of ST-elevated myocardial infarction (odds ratio [OR] = 5.855, 95% confidence interval [CI] = 1.391–24.635, p = 0.016), follow-up low-density lipoprotein cholesterol level (OR = 6.832, 95% CI = 2.103–22.200, p = 0.001), baseline low-attenuation plaque (OR = 7.311, 95% CI = 1.242–43.028, p = 0.028) and EAT (OR = 1.015, 95% CI = 1.000–1.029, p = 0.044). Following the second CCTA examination, major adverse cardiac events (MACEs) were observed in 12 patients, and NCL plaque progression was significantly associated with future MACEs (log rank p = 0.006). CONCLUSION: Noninvasive assessment of NCLs by CCTA has potential prognostic value.

Hypoxic preconditioning inhibits apoptosis of bone marrow mesenchymal stem cells through overexpressing Pim-1 / 中国组织工程研究

BACKGROUND:Bone marrow mesenchymal stem cel s have a low survival rate after implanted into the ischemic myocardium. However, hypoxia preconditioning (HPC) may enhance bone marrow mesenchymal stem cel proliferation and promote its survival rate. OBJECTIVE:To explore whether Pim-1 is involved in HPC protecting against apoptosis of bone marrow mesenchymal stem cel s and the relevant mechanism. METHODS:Bone marrow mesenchymal stem cel s were respectively subjected to HPC for 0, 6, 12, and 24 hours. The expression of Pim-1 and apoptosis-related genes were detected by RT-qPCR and western blot. Then, the best hypoxic preconditioning time was determined as 12 hours. Then, bone marrow mesenchymal stem cel s were assigned to one of the fol owing groups:control (without HPC), 12-hour HPC, 12-hour HPC+Pim-1 inhibitor groups. Flow cytometry analysis was used to detect the cel apoptosis, Transwel assay to analyze the cel migration ability in each group, and JC-1 kit to detect mitochondrial membrane potential. Animal models of myocardial infarction were established. One week after modeling, bone marrow mesenchymal stem cel s were given via multi-point injection around the infarct zone of rats. Two weeks after modeling, heart tissues of rats were taken and sliced fol owed by DiI staining to calculate the survival rate of bone marrow mesenchymal stem cel s. Additional y, rat cardiac function was assessed by echocardiography prior to and after modeling as wel as at 4 weeks after cel transplantation. RESULTS AND CONCLUSION:At 12 hours after HPC, the expression of Pim-1, p-Akt and Bcl-2 gene in the infarct region was significantly increased, but the expression of caspase-3 and Bax was significantly decreased. Compared with the control group, cel viability in the 12-hour HPC group was increased very significantly at 1 week after cel transplantation (P<0.001), the migration and anti-apoptosis ability were enhanced significantly (P<0.01) and the cardiac function of rats was significantly improved in the 12-hour HPC group (P<0.05). Al of these protective effects were blocked by the Pim-1 inhibitor. These findings indicate that HPC can protect bone marrow mesenchymal stem cel s from apoptosis through activating Akt and up-regulating Pim-1, and thereby improve the therapeutic effect of bone marrow mesenchymal stem cel transplantation on ischemic heart diseases.