[This corrects the article DOI: 10.1016/j.apsb.2021.07.006.].

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide

Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2−/− and Ampkα2−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser485), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser485), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.

BACKGROUND: Early neurologic deterioration (END) may occur in patients with anterior circulation ischemic stroke (ACIS) after receiving endovascular treatment (EVT). Hemodynamic insufficiency, re-occlusion, and post-re-canalization hyper-perfusion are likely to play a critical role in END. We hypothesized that hemodynamic changes can predict END in patients with ACIS post-successful EVT using trans-cranial Doppler (TCD). METHODS: We utilized a prospectively maintained database of ACIS patients treated with EVT between September 2016 and June 2018 in the Xuanwu Hospital, Capital Medical University. TCD parameters including peak systolic velocity (PSV), bilateral mean flow velocity (MFV), and pulse index (PI) were determined via the middle cerebral arteries within 72 h post-EVT. A logistic regression model was applied to detect independent predictors for END. RESULTS: Totally, 112 EVT patients were included in this study and 80/112 patients experienced successful re-canalization with <50% residual stenosis, while 17/80 (21.3%) patients suffered END, for which vasogenic cerebral edema (11/17) was considered as a leading role and followed by symptomatic intra-cranial hemorrhage (4/17) and ischemia progression (2/17). For the 80 patients, the PSV (median: 127 cm/s vs. 116 cm/s, P = 0.039), the ratio of ipsilateral-MFV/contra-lateral-MFV (iMFV/cMFV) (median: 1.29 vs. 1.02, P = 0.036) and iMFV/mean blood pressure (MBP) (median: 0.97 vs. 0.79, P = 0.008) in END patients were higher than those of non-END. Using the receiver-operating characteristic curve to obtain cut-off values for PSV, PI, iMFV/cMFV, and iMFV/MBP for END, we found that PI ≥0.85 (odds ratio: 11.03, 95% confidence interval: 1.92-63.46, P = 0.007) and iMFV/MBP ≥0.84 (odds ratio: 9.20, 95% confidence interval: 2.07-40.84, P = 0.004) were independent predictors of END in a multivariate logistic regression model, with a sensitivity of 82.4% and 76.5% and a specificity of 42.9% and 66.7%, respectively, and had the positive predictive values of 29.0% and 38.2%, and negative predictive values of 90.0% and 91.3%, with an area under the receiver-operating characteristic curve of 0.57 and 0.71, respectively. CONCLUSION TCD examination of EVT patients may be used as a real-time tool to detect END predictors, such as the higher PI and iMFV/MBP, allowing for better post-thrombectomy management in ACIS patients.

BACKGROUND: Asymptomatic coronary artery stenosis (ACAS) ≥50% is common in patients with acute ischemic cerebrovascular disease (AICVD), which portends a poor cardiovascular and cerebrovascular prognosis. Identifying ACAS ≥50% early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients. This study aimed to investigate whether aortic arch plaque (AAP), an early atherosclerotic manifestation of brain blood-supplying arteries, could be a predictor for ACAS ≥50% in AICVD. METHODS: In this cross-sectional study, atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography (CTA) in AICVD patients without coronary artery disease history. The patients were divided into ACAS ≥50% and non-ACAS ≥50% groups according to whether CTA showed stenosis ≥50% in at least one coronary arterial segment. The AAP characteristics of CTA were depicted from aspects of thickness, extent, and complexity. RESULTS: Among 118 analyzed patients with AICVD, 29/118 (24.6%) patients had ACAS ≥50%, while AAPs were observed in 86/118 (72.9%) patients. Increased AAP thickness per millimeter (adjusted odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.18-2.05), severe-extent AAP (adjusted OR: 13.66, 95% CI: 2.33-80.15), and presence of complex AAP (adjusted OR: 7.27, 95% CI: 2.30-23.03) were associated with ACAS ≥50% among patients with AICVD, independently of clinical demographics and cervicocephalic atherosclerotic stenosis. The combination of AAP thickness, extent, and complexity predicted ACAS ≥50% with an area under the receiver-operating characteristic curve of 0.78 (95% CI: 0.70-0.85, P < 0.001). All three AAP characteristics provided additional predictive power beyond cervical and intracranial atherosclerotic stenosis for ACAS ≥50% in AICVD (all P < 0.05). CONCLUSIONS Thicker, severe-extent, and complex AAP were significant markers of the concomitant ACAS ≥50% in AICVD, possibly superior to the indicative value of cervical and intracranial atherosclerotic stenosis. As an integral part of atherosclerosis of brain blood-supplying arteries, AAP should not be overlooked in predicting ACAS ≥50% for patients with AICVD.
Aged ; Aorta, Thoracic ; pathology ; Cerebrovascular Disorders ; diagnosis ; Coronary Stenosis ; diagnosis ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Odds Ratio ; Plaque, Atherosclerotic ; diagnosis ; Risk Factors

BACKGROUND: No head to head comparison is available between surgical lip lifting and upper lip filler injections to decide which technique yields the best results in patients. Despite the growing popularity of upper lip augmentation, its effect on societal perceptions of attractiveness, successfulness and overall health in woman is unknown. METHODS: Blinded casual observers viewed three versions of independent images of 15 unique patient lower faces for a total of 45 images. Observers rated the attractiveness, perceived success, and perceived overall health for each patient image. Facial perception questions were answered on a visual analog scale from 0 to 100, where higher scores corresponded to more positive responses. RESULTS: Two hundred and seventeen random observers with an average age of 47 years (standard deviation, 15.9) rated the images. The majority of observers were females (n=183, 84%) of white race (n=174, 80%) and had at least some college education (n=202, 93%). The marginal mean score for perceived attractiveness from the natural condition was 1.5 points (95% confidence interval [CI], 0.9–2.18) higher than perceived attractiveness from the simulated upper lip filler injection condition, and 2.6 points higher (95% CI, 1.95–3.24) than the simulated upper lip lift condition. There was a moderate to strong correlation between the scores of the same observer. CONCLUSIONS: Simulated upper lip augmentation is amenable to social perception analysis. Scores of the same observer for attractiveness, successfulness, and overall health are strongly correlated. Overall, the natural condition had the highest scores in all categories, followed by simulated upper lip filler, and lastly simulated upper lip lift.
Continental Population Groups ; Education ; Female ; Head ; Humans ; Lifting ; Lip ; Photography ; Social Perception ; Surgery, Plastic ; Visual Analog Scale

Asthma is the most common chronic pulmonary disease worldwide and places a considerable economic burden on society. China is the world's largest developing country and has the largest population. China has undergone dramatic changes in the past few decades. The traditional lifestyle and living environment have changed in ways that directly affect the prevalence of asthma. The prevalence of asthma is lower in Chinese children and adults than in developed countries, but the prevalence has been on the rise during the past 30 years. The prevalence significantly varies among different parts of China. Polymorphisms of multiple genes, outdoor air pollution caused by PM2.5, PM10, SO2, NO2, environmental tobacco smoke, and coal, indoor pollution, and inhaled allergens, such as house dust mites, pollen, and cockroach particles, are risk factors for asthma.
Adult ; Air Pollution ; Allergens ; Asian Continental Ancestry Group ; Asthma* ; Child ; China* ; Coal ; Cockroaches ; Developed Countries ; Developing Countries ; Environmental Exposure* ; Genetic Predisposition to Disease* ; Humans ; Life Style ; Lung Diseases ; Pollen ; Polymorphism, Genetic ; Prevalence ; Pyroglyphidae ; Risk Factors* ; Smoke ; Tobacco

Aedes ; virology ; Animals ; China ; epidemiology ; Genetic Variation ; Genome, Viral ; Humans ; Multigene Family ; Viral Proteins ; genetics ; Zika Virus ; classification ; genetics ; isolation & purification ; Zika Virus Infection ; epidemiology ; virology

BACKGROUNDThe difference in clinical outcome between paclitaxal-eluting stents (PES) and sirolimus-eluting stents with bio-degradable polymer (SES-BDP) for bifurcation lesions remains unclear. The present study aimed to investigate the one-year clinical outcome after DK crush stenting using PES (Taxus(TM)) vs. SES-BDP (Excel(TM)) from our database.

METHODSA total of 275 patients (90 from the DKCRUSH-I and 185 from the DKCRUSH-II study) were studied. The primary endpoint was the occurrence of major adverse cardiac events (MACE) at 12 months; including cardiac death, myocardial infarction (MI), or target vessel revascularization (TVR). The rate of binary restenosis and stent thrombosis served as secondary endpoints.

RESULTSAt follow-up, minimal luminal diameter (MLD) in the Taxus group was (2.11 ± 0.66) mm, with resultant increased target lesion revascularization (TLR) 12.2% and TVR 14.4%, significantly different from the Excel group; (2.47 ± 0.56) mm, P < 0.001, 3.2%, P = 0.006, 4.9%, P = 0.019, respectively. As a result there was a significant difference in MACE between the Taxus (20.0%) and Excel (10.3%, P = 0.038) groups. Overall stent thrombosis was monitored in 11 patients (4.0%), with five in the Excel group (2.7%) and six in the Taxus group (6.7%). All stent thrombosis in the Excel group was classified as early, and all were defined as late in the Taxus group.

CONCLUSIONThe Excel stent had lower rate of stent thrombosis, TLR, TVR, and composite MACE at 12-month after an indexed stenting procedure, compared to the Taxus stent.

Absorbable Implants ; Aged ; Coronary Artery Disease ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Paclitaxel ; therapeutic use ; Polymers ; Sirolimus ; therapeutic use

BACKGROUNDDurable polymers used for first-generation drug-eluting stents (DES) potentially contribute to persistent inflammation and late DES thrombosis. We report the first in human experience with the rapamycin-eluting biodegradable polymer coated cobalt-chromium FIREHAWK stent with abluminal groove.

METHODSA total of 21 patients with stable or unstable angina, or prior myocardial infarction, with single de novo native coronary stenoses < 30 mm in length in vessel sizes ranging from 2.25 to 4.0 mm were enrolled. The primary endpoint was major adverse cardiac events (MACE) at 30 days defined as the composite of cardiac death, myocardial infarction (Q and non-Q), or ischemia-driven target lesion revascularization. Secondary endpoints include device, lesion, and clinical success rates, 4-month in-stent late lumen loss by quantitative coronary angiography (QCA), proportion of uncovered or malapposed stent struts by optical coherence tomograpphy (OCT) at 4 months, and MACE at 4, 12, 24 and 36-month follow-up.

RESULTSDevice success was 95.7%, lesion and clinical success was 100.0%. There were no MACE events at 30 days. One patient died of non-cardiac hemorrhagic stroke 5 days after index procedure. At 4 months, in-stent late loss was (0.13 ± 0.18) mm, and complete strut coverage was 96.2% by OCT with 0.1% strut malapposition. At 4-month follow-up there was no additional MACE events, and a single target vessel (non-target lesion) revascularization.

CONCLUSIONSThe FIREHAWK abluminal groove biodegradable polymer rapamycin-eluting stent demonstrated feasibility, safety and efficacy in this first in human experience. OCT findings indicated excellent stent strut coverage 4 months after implantation. Larger studies are required to confirm whether the early FIREHAWK stent results translate into longer term restenosis and thrombosis benefits.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Coronary Artery Disease ; therapy ; Drug-Eluting Stents ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Polymers ; administration & dosage ; Sirolimus ; administration & dosage ; Tomography, Optical Coherence