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1.
J Hazard Mater ; 421: 126799, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34396958

RESUMO

Stack aerosols are generated within vertical building drainage stacks during the discharge of wastewater containing feces and exhaled mucus from toilets and washbasins. Fifteen stack aerosol-related outbreaks of coronavirus disease 2019 (COVID-19) in high-rise buildings have been observed in Hong Kong and Guangzhou. Currently, we investigated two such outbreaks of COVID-19 in Hong Kong, identified the probable role of chimney effect-induced airflow in a building drainage system in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We injected tracer gas (SF6) into the drainage stacks via the water closet of the index case and monitored tracer gas concentrations in the bathrooms and along the facades of infected and non-infected flats and in roof vents. The air temperature, humidity, and pressure in vertical stacks were also monitored. The measured tracer gas distribution agreed with the observed distribution of the infected cases. Phylogenetic analysis of the SARS-CoV-2 genome sequences demonstrated clonal spread from a point source in cases along the same vertical column. The stack air pressure and temperature distributions suggested that stack aerosols can spread to indoors through pipe leaks which provide direct evidence for the long-range aerosol transmission of SARS-CoV-2 through drainage pipes via the chimney effect.


Assuntos
Aerossóis , Microbiologia do Ar , COVID-19 , Habitação , COVID-19/transmissão , Hong Kong , Humanos , Filogenia , SARS-CoV-2
2.
Dev Comp Immunol ; 127: 104306, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34736993

RESUMO

Protein Kinase A catalytic subunit α (PKACα), plays an important role in the PKA and NF-κB signaling pathway in mammals. However, the function of PKACα in teleost fish remains largely unknown. In this study, PKACα from black carp (bcPKACα) has been cloned and its role in the innate immune antiviral signaling pathway was investigated. The open reading frame of bcPKACα gene contains 1056 nucleotides and the immunofluorescence assay verified that PKACα was mainly distributed in the cytoplasm. The reporter assay showed that bcPKACα expression and co-expression of bcPKACα and black carp TAK1 (bcTAK1) could activate the transcription of NF-κB. However, bcTAK1/bcIRF7-mediated IFN transcription was inhibited by bcPKACα. Knockdown of bcPKACα showed slightly enhanced antiviral activity against spring viremia of carp virus (SVCV) compared with control group. Accordingly, the antiviral activity against SVCV and grass carp reovirus (GCRV) of EPC cells co-expressing bcPKACα, bcTAK1 and bcIRF7 was obviously lower than that of EPC cells co-expressing bcTAK1 and bcIRF7. The similar subcellular distribution and interaction between bcPKACα and bcTAK1 were detected by immunofluorescent staining and co-immunoprecipitation assay separately. The data generated in this study demonstrates that bcPKACα associates with bcTAK1 and positively regulates NF-κB signaling, however, negatively regulates TAK1/IRF7 signaling pathway.

3.
Dev Comp Immunol ; 127: 104310, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34762938

RESUMO

The myeloid differentiation factor 2 (MD-2)-related lipid recognition (ML) domain is present in MD-2, MD-1, GM2-activator protein (GM2A) and Niemann-Pick disease type C2 (NPC2). ML proteins function in antibacterial signal transduction and lipid metabolism in vertebrates, but the mechanism in invertebrates is unknown. In this study, we found that ML proteins were involved in bacterial resistance in Chinese mitten crab (Eriocheir sinensis). One member, EsML3, a soluble, bacterial-induced pattern recognition protein was upregulated in hemocytes following bacterial challenge. Recombinant EsML3 bound to Gram-negative bacteria (Vibrio parahaemolyticus) and Gram-positive bacteria (Staphylococcus aureus) by interaction with peptidoglycan, lipopolysaccharide. EsML3 showed no direct bacteriostatic or bacteriocidal activity. Pre-incubating bacteria with rEsML3 significantly promoted in vivo bacterial clearance. EsML3 also promoted phagocytic activity and plays a role against bacterial infection. In summary, EsML3 mediates cellular immune responses by recognising invasive microorganisms, promoting bacterial clearance and phagocytosis against bacterial infection in crab.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34849938

RESUMO

OBJECTIVES: The cervicothoracic junction is a special section that connects the neck, thoracic cavity, mediastinum and axilla. Tumours in the region often invade or compress surrounding tissues and organs, which makes the surgical treatment difficult. METHODS: A retrospective analysis involving 69 patients with tumours at the cervicothoracic junction. Clinical data with regard to manifestation, surgical approach, resection degree, outcome and pathological types were collected. RESULTS: A total of 48 cases of asymptomatic patients and 21 cases of patients with ≥1 clinical manifestation were enrolled in the study. Twenty-seven patients received radical resection with video-assisted thoracoscopic surgery. Anterior approach was the predominant treatment method in open surgery (25 cases, 36.2%), while the anterolateral approach was used in 8 cases (6 cases of hemiclamshell incisions and 2 cases of trap-door incisions). In addition, we observed 1 case of posterior approach, 2 cases of posterolateral approach and 1 case of supraclavicular approach combined with posterolateral approach. Pathological examination results revealed 67 cases of radical resection and 2 cases of microscopic residual. Neurilemmoma was the most widespread pathological type (30 cases, 43.5%), followed by tumour originating from fibrous tissues (5 cases, 7.2%). A 3-year overall survival rate of the 69 patients was 89.9%, while a 5-year overall survival rate was 85.5%. CONCLUSIONS: Tumours associated with the cervicothoracic junction are characterized by their unique location, complex anatomy and various histopathological subtypes. An individualized approach during surgery enhances safety and standardized of treatments for patients with tumours located at the cervicothoracic junction.

5.
J Pharm Pharmacol ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34850055

RESUMO

OBJECTIVES: Myocardial I/R injury is one of the most serious complications after reperfusion therapy in patients with myocardial infarction. Remifentanil has been found to protect the heart against I/R injury. However, its underlying mechanism remains uncertain in myocardial I/R injury. METHODS: The myocardial I/R injury rat model was established by 30 min of ischaemia followed by 24 h of reperfusion. The animal model was evaluated by the levels of TC, ALT and AST and H&E staining. The binding of miR-206-3p and TLR4 was predicted and verified using TargetScan software, luciferase reporter and RNA pull-down assays. The functional role and mechanism of remifentanil were identified by ultrasonic echocardiography, oxidative stress markers, H&E, Masson and TUNEL staining and western blot. KEY FINDINGS: The rat myocardial I/R injury model displayed a significantly high level of TC, ALT, AST, TLR4, p-IκBα and p-p65 and the presence of disorganized cells and inflammatory cell infiltration. The model also showed increased levels of LVEDD, LVESD, MDA, fibrosis and apoptosis and decreased levels of EF, FS, SOD and GSH, which were reversed with remifentanil treatment. Knockdown of miR-206-3p damaged cardiac function and aggravated oxidative stress. miR-206-3p could directly bind to TLR4. TLR4 overexpression destroyed cardiac function, exacerbated oxidative stress, increased levels of p-IκBα and p-p65 and aggravated pathology manifestation affected by remifentanil. CONCLUSIONS: Our results elucidated that remifentanil alleviated myocardial I/R injury by miR-206-3p/TLR4/NF-κB signalling axis.

6.
Front Pharmacol ; 12: 761641, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744741

RESUMO

Safflower polysaccharide (SPS) is one of the active fractions extracted from safflower petals (Carthamus tinctorius L.) which has been reported to possess antitumor and immune control roles. However, its antitumor mechanisms by regulating the immune pathway remain barely understood. In this study, a mouse model was established by azoxymethane (AOM)/dextran sodium sulfate (DSS) to evaluate the antitumor effect of SPS on colorectal cancer (CRC). The results showed that 50 mg/kg SPS-1, an active fraction isolated from SPS, could significantly inhibit CRC induced by AOM/DSS and changed the polarization of macrophages to the M1 phenotype. Meanwhile, SPS-1 treatment significantly alleviated the characteristic AOM/DSS-induced pathological symptoms, in terms of decreasing the nucleoplasmic ratio, nuclear polarity extinction, and gland hyperplasia. However, the results in vitro showed that SPS-1 did not directly inhibit the growth of CRC cells but could upregulate the NF-κB signal and trigger M1 macrophage transformation. Thus, the condition medium (CM) of Mφ pretreated with SPS-1 was used against CRC cells. As expected, SPS-1-activated Raw 264.7 markedly exhibited antitumor effects by inhibiting cell proliferation and suppressing cell colony formation. In addition, SPS-1-activated Raw 264.7 could also induce CRC cell apoptosis by upregulating the levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further results suggested that SPS-1-induced transition of the macrophage phenotype could be suppressed by an NF-κB inhibitor, PDTC. Moreover, SPS-1-activated Raw 264.7 inhibiting CRC cell proliferation and inducing apoptosis were also rescued by PDTC. Taken together, all results suggested that SPS-1 could be a therapeutic option for the prevention and treatment of CRC.

7.
J BUON ; 26(5): 1815-1823, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34761588

RESUMO

PURPOSE: We analyzed the relationship between clinical data, tumor markers, chest high-resolution CT(HRCT) and pathology in patients with solitary pulmonary nodules (SPN) and explored the joint discrimination scheme to improve the accuracy of noninvasive diagnosis. METHODS: 242 SPNs with the largest diameter D<2cmwere divided into training set (161 cases) and test set (81 cases). We screened the risk factors by single factor analysis. Then, we established the prediction equation model (PE model) based on logistic regression and malignant tendency comprehensive score model (MTCS model) based on the evaluation criteria of SPN. The weight of the two sub models was used to determine the joint evaluation model (JE model). RESULTS: Age, CEA content, maximum diameter, pleural adhesions, spicule sign, and ground glass component were independent factors of malignant prediction (p<0.05) recorded as x1~x6, and PE model was established as P1=ex/(1+ex),x=0.052x1+0.0327x2+0.212x3+1.849x4+ 1.066x5+1.769x6-7.582.According to the different performance of different manifestations of the corresponding score, we could get each score S of SPN. The MTCS model was S/8.5. The JE model was P=0.76P1+0.24S/8.5. The results of test set showed the AUC values of JE, PE, MTCS, Mayo, VA and Li Yun model for D≤2cm SPN were 0.930(95% CI:0.877-0.983), 0.922(95% CI:0.870-0.974), 0.900(95% CI:0.879-0.921), 0.782(95% CI:0.749-0.815), 0.744(95% CI:0.731-0.756) and 0.801(95% CI:0.739-0.863). The sensitivity of JE, PE, MTCS model were 87.2%, 79.2%, 73.3%, the specificity was 90.1%, 89.2%, 82.2%, and the accuracy was 89.9%, 85.5%, 81.2%. CONCLUSIONS: The joint evaluation model has better diagnostic efficiency and can provide reference for the diagnosis of SPN with D≤2cm.

8.
Front Physiol ; 12: 719753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759831

RESUMO

Ischemia-reperfusion (I/R) injury contributes to the morbidity and mortality of ischemic strokes. As an in vitro model, oxygen-glucose deprivation and reperfusion (OGD/R) exposure induces neuronal injury. Low-dose ethanol preconditioning (EtOH-PC) was reported to alleviate neuronal apoptosis during OGD/R. However, whether the mitochondrial BKCa (mitoBKCa) channel is involved in the neuroprotective effect of EtOH-PC during OGD/R is not clearly defined. This study attempts to explore the mediation of the mitoBKCa channel in the neuroprotective effect of EtOH-PC on OGD/R-induced neuronal apoptosis and the underlying mechanisms. OGD/R model was established using primary cortical neurons that were preincubated with ethanol. Subsequently, the cell viability was measured by CCK-8 assay, and the apoptotic cells were determined by TUNEL assay. Annexin V/7-AAD staining and mitochondrial membrane potential using JC-10 were detected by flow cytometry. Western blot analysis was performed to check the apoptosis-related proteins. In the mixed primary culture, 95% neurofilament-positive cells were cortical neurons. Low-dose EtOH-PC (10 mmol/L) for 24 h significantly attenuated the OGD2h/R24h-induced neuronal apoptosis through activating the BKCa channel. Further investigations suggested that ethanol pretreatment increased the mitochondrial membrane potential (MMP) and downregulated the production of cleaved caspase 3 in OGD/R-injured neurons by activating the mitoBKCa channel. Low-dose ethanol pretreatment significantly attenuated the OGD/R-induced neuronal apoptosis mediated by the mitoBKCa channel which modulated the mitochondrial function by impeding the uncontrolled opening of mitochondrial permeability transition pore (MPTP).

9.
Cell Death Dis ; 12(11): 1077, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772918

RESUMO

Depression is one of the most common psychiatric disorders. Recently, studies demonstrate that antidepressants generating BDNF not only maintain synaptic signal transmission but also repress neuroinflammatory cytokines such as IL-6 and IL-1ß. Therefore, promoting BDNF expression provides a strategy for the treatment of depression. Our recent research has indicated that programmed cell death 4 (Pdcd4) is a new target for antidepressant treatment by facilitating BDNF. Herein, we modified Pdcd4 specific small interfering RNA (siPdcd4) with the rabies virus glycoprotein peptide (RVG/siPdcd4) which enables it cross the blood-brain barrier (BBB). We found that RVG/siPdcd4 complex was selectively delivered to neurons and microglia and silenced the expression of Pdcd4, thereby up-regulating the level of BDNF and down-regulating IL-6 and IL-1ß expression. More importantly, RVG/siPdcd4 injection attenuated synaptic plasticity impairment and protected mice from CRS-induced depressive behavior. These findings suggest that RVG/siPdcd4 complex is a potential therapeutic medicine for depression.

10.
Nat Commun ; 12(1): 6450, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750392

RESUMO

The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.

11.
CNS Neurosci Ther ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837479

RESUMO

AIMS: To identify the metabolic pattern and prognostic predictors in anti-gamma-aminobutyric-acid B (GABAB) receptor encephalitis using 18 F-fluorodeoxy-glucose positron emission tomography (18 F-FDG-PET). METHODS: Twenty-one patients diagnosed anti-GABAB receptor encephalitis who underwent 18 F-FDG-PET at first hospitalization were retrospectively reviewed. 18 F-FDG-PET images were analyzed in comparison with controls. Further group comparisons of 18 F-FDG-PET data were carried out between prognostic subgroups. RESULTS: 18 F-FDG-PET was abnormal in 81% patients with anti-GABAB receptor encephalitis and was more sensitive than MRI (81% vs. 42.9%, p = 0.025). Alter limbic lobe glucose metabolism (mostly hypermetabolism) was observed in 14 patients (66.7%), of whom 10 (10/14, 71.4%) demonstrated hypermetabolism in the medial temporal lobe (MTL). Group analysis also confirmed MTL hypermetabolism in association with relative frontal and parietal hypometabolism was a general metabolic pattern. After a median follow-up of 33 months, the group comparisons revealed that patients with poor outcome demonstrated increased metabolism in the MTL compared to those with good outcome. CONCLUSION: 18 F-FDG-PET may be more sensitive than MRI in the early diagnosis of anti-GABAB receptor encephalitis. MTL hypermetabolism was associated with relative frontal or parietal hypometabolism and may serve as a prognostic biomarker in anti-GABAB receptor encephalitis.

12.
Dev Comp Immunol ; 128: 104313, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34762937

RESUMO

Down syndrome cell adhesion molecule (Dscam), also called hypervariable Dscam (Dscam-hv), is an important player in arthropod alternative splicing that connects neurons and immune regulation, acting as a pathogen-specific recognition molecule. Dscam-hv has two forms: transmembrane (TM) Dscam (mDscam) and soluble Dscam (sDscam). Herein, we investigated two transmembrane variants of mDscam resulting from alternative splicing of the transmembrane domain, focusing on differences in their immune regulation. We characterized the Dscam[TM1] and Dscam[TM2] genes of Chinese mitten crab (Eriocheir sinensis) through bioinformatics analysis. Both genes are expressed in the gill, intestine, and other immune tissues. Following gram-positive and gram-negative bacteria stimulation, EsDscam[TM1] and EsDscam[TM2] mRNA expression levels increased significantly in hemocytes. Sequencing showed that EsDscam[TM1] was more abundant in hemocytes than EsDscam[TM2]. Additionally, the two subtypes differ in their regulation of antimicrobial peptides, the proportion of exon 33 carried, and bacterial phagocytosis.

13.
J Thorac Oncol ; 16(12): e97-e98, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34809806
14.
Mov Disord ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34820915

RESUMO

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

15.
Front Neurol ; 12: 640526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721249

RESUMO

Accurately identifying epileptogenic zone (EZ) using high-frequency oscillations (HFOs) is a challenge that must be mastered to transfer HFOs into clinical use. We analyzed the ability of a convolutional neural network (CNN) model to distinguish EZ and non-EZ HFOs. Nineteen medically intractable epilepsy patients with good surgical outcomes 2 years after surgery were studied. Five-minute interictal intracranial electroencephalogram epochs of slow-wave sleep were selected randomly. Then 5 s segments of ripples (80-200 Hz) and fast ripples (FRs, 200-500 Hz) were detected automatically. The EZs and non-EZs were identified using the surgery resection range. We innovatively converted all epochs into four types of images using two scales: original waveforms, filtered waveforms, wavelet spectrum images, and smoothed pseudo Wigner-Ville distribution (SPWVD) spectrum images. Two scales were fixed and fitted scales. We then used a CNN model to classify the HFOs into EZ and non-EZ categories. As a result, 7,000 epochs of ripples and 2,000 epochs of FRs were randomly selected from the EZ and non-EZ data for analysis. Our CNN model can distinguish EZ and non-EZ HFOs successfully. Except for original ripple waveforms, the results from CNN models that are trained using fixed-scale images are significantly better than those from models trained using fitted-scale images (p < 0.05). Of the four fixed-scale transformations, the CNN based on the adjusted SPWVD (ASPWVD) produced the best accuracies (80.89 ± 1.43% and 77.85 ± 1.61% for ripples and FRs, respectively, p < 0.05). The CNN using ASPWVD transformation images is an effective deep learning method that can be used to classify EZ and non-EZ HFOs.

16.
Front Immunol ; 12: 746585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721416

RESUMO

Irritable bowel syndrome with diarrhea and functional diarrhea are both functional bowel disorders that cause chronic diarrhea. Chronic diarrhea is closely related to daily life and the psychological condition of diarrhea in patients, and probiotics can play a significant role in alleviating chronic diarrhea in some research. Lactobaccilus plantarum CCFM1143 can relieve diarrhea in mice caused by enterotoxigenic Escherichia coli (ETEC); however, its clinical effects remain unclear. This study aimed to assess the effects of CCFM1143 as a therapy for chronic diarrhea patients. Fifty-five patients with chronic diarrhea were randomly assigned into the probiotic group (n = 28) and the placebo group (n = 27), receiving the routine regimen with or without probiotics for 4 weeks, respectively. CCFM1143 can mitigate the apparent clinical symptoms and improve the health status and quality of life of patients. In addition, it could inhibit the increase in interleukin 6 (IL-6) and the decrease in motilin; modulate the short-chain fatty acids, especially acetic and propionic acids; and regulate the gut microbiota, particularly reducing the abundance of Bacteroides and Eggerthella and enriching the abundance of Akkermansia, Anaerostipes, and Terrisporobacter. In addition, treatment with probiotics showed clinical effectiveness in managing chronic diarrhea when compared with the placebo group. The findings could help to develop and further the application of probiotics for chronic diarrhea.

17.
Front Cardiovasc Med ; 8: 719755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722657

RESUMO

Background: The aim of this study was to investigate the efficacy of left atrial appendage closure (LAAC) for primary and secondary stroke prevention in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). Methods: This pilot study enrolled 36 patients with HCM and AF who underwent LAAC between April 2017 and December 2019, of whom 22 were for primary stroke prevention and 14 were for secondary prevention. Results: The patients enrolled in this study had non-obstructive (86.1%) or mild obstructive (13.9%) HCM. Patients in the Secondary Prevention Group had higher CHA2DS2-VASc scores (5.1 ± 1.4 vs. 2.6 ± 1.6, P < 0.001) and higher HAS-BLED scores (2.8 ± 1.0 vs. 1.5 ± 0.9, P < 0.001) compared with those in the Primary Prevention Group. Successful closure with satisfactory seals (residual leak ≤ 5 mm) was achieved in all patients, with complete occlusion in 86.4% of the Primary Prevention Group and 92.9% of the Secondary Prevention Group. Procedural-related complications included one pericardial effusion and one groin hematoma. One device-related thrombus was identified in the Secondary Prevention Group and resolved after anticoagulation. During a mean follow-up time of 28.4 months, one bleeding event was recorded. There were no thromboembolic events or deaths in either group, with 97.2% of the patients achieving freedom from anticoagulation therapy. Conclusions: Initial results suggest that LAAC can be a safe and feasible alternative for primary and secondary stroke prevention in selected patients with HCM and AF. Further studies with larger samples are required.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34837101

RESUMO

Metformin has been found to have inhibitory effects on a variety of tumors. However, its effects on non-small cell lung cancer (NSCLC) remain unclear. We demonstrated that metformin could inhibit the proliferation of A549 and H1299 cells. RNA transcriptome sequencing revealed that PDL1 was significantly downregulated in both cell types following treatment with metformin (P < 0.001). Jaspar analysis and chromatin immunoprecipitation showed that CEBPB could directly bind the promoter region of PDL1. Western blotting showed that protein expression of the isoforms CEBPB-LAP*, CEBPB-LAP, and CEBPB-LIP was significantly upregulated and the LIP/LAP ratio was increased. Gene chip analysis showed that PDL1 was significantly upregulated in A549-CEBPB-LAP cells and significantly downregulated in A549-CEBPB-LIP cells (P < 0.05) compared with CEBPB-NC cells. Dual-luciferase reporter gene assay showed that CEBPB-LAP overexpression could promote transcription of PDL1 and CEBPB-LIP overexpression could inhibit the process. Functional assays showed that the changes in CEBPB isoforms affected the function of NSCLC cells. Western blotting showed that metformin could regulate the function of NSCLC cells via AMPK-CEBPB-PDL1 signaling. Animal experiments showed that tumor growth was significantly inhibited by metformin, and atezolizumab and metformin had a synergistic effect on tumor growth. A total of 1247 patients were retrospectively analyzed, including 166 and 1081 patients in metformin and control groups, respectively. The positive rate of PDL1 was lower than that of the control group (HR = 0.338, 95% CI = 0.235-0.487; P < 0.001). In conclusion, metformin inhibited the proliferation of NSCLC cells and played an anti-tumor role in an AMPK-CEBPB-PDL1 signaling-dependent manner.

19.
Front Neurol ; 12: 687931, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777193

RESUMO

Objective: Skull fractures caused by head trauma can lead to life-threatening complications. Hence, timely and accurate identification of fractures is of great importance. Therefore, this study aims to develop a deep learning system for automated identification of skull fractures from cranial computed tomography (CT) scans. Method: This study retrospectively analyzed CT scans of 4,782 patients (median age, 54 years; 2,583 males, 2,199 females; development set: n = 4,168, test set: n = 614) diagnosed with skull fractures between September 2016 and September 2020. Additional data of 7,856 healthy people were included in the analysis to reduce the probability of false detection. Skull fractures in all the scans were manually labeled by seven experienced neurologists. Two deep learning approaches were developed and tested for the identification of skull fractures. In the first approach, the fracture identification task was treated as an object detected problem, and a YOLOv3 network was trained to identify all the instances of skull fracture. In the second approach, the task was treated as a segmentation problem and a modified attention U-net was trained to segment all the voxels representing skull fracture. The developed models were tested using an external test set of 235 patients (93 with, and 142 without skull fracture). Results: On the test set, the YOLOv3 achieved average fracture detection sensitivity and specificity of 80.64, and 85.92%, respectively. On the same dataset, the modified attention U-Net achieved a fracture detection sensitivity and specificity of 82.80, and 88.73%, respectively. Conclusion: Deep learning methods can identify skull fractures with good sensitivity. The segmentation approach to fracture identification may achieve better results.

20.
Front Cardiovasc Med ; 8: 757022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778409

RESUMO

Aortic dissection (AD) is a catastrophic cardiovascular emergency with a poor prognosis, and little preceding symptoms. Abnormal lipid metabolism is closely related to the pathogenesis of AD. However, comprehensive lipid alterations related to AD pathogenesis remain unclear. Moreover, there is an urgent need for new or better biomarkers for improved risk assessment and surveillance of AD. Therefore, an untargeted lipidomic approach based on ultra-high-performance liquid chromatograph-mass spectrometry was employed to unveil plasma lipidomic alterations and potential biomarkers for AD patients in this study. We found that 278 of 439 identified lipid species were significantly altered in AD patients (n = 35) compared to normal controls (n = 32). Notably, most lipid species, including fatty acids, acylcarnitines, cholesteryl ester, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, lysophosphatidylethanolamines, phosphatidylcholines, phosphatidylinositols, diacylglycerols, and triacylglycerols with total acyl chain carbon number ≥54 and/or total double bond number ≥4 were decreased, whereas phosphatidylethanolamines and triacylglycerols with total double bond number <4 accumulated in AD patients. Besides, the length and unsaturation of acyl chains in triacylglycerols and unsaturation of 1-acyl chain in phosphatidylethanolamines were decreased in AD patients. Moreover, lysophosphatidylcholines were the lipids with the largest alterations, at the center of correlation networks of lipid alterations, and had excellent performances in identifying AD patients. The area under the curve of 1.0 and accuracy rate of 100% could be easily obtained by lysophosphatidylcholine (20:0/0:0) or its combination with lysophosphatidylcholine (17:0/0:0) or lysophosphatidylcholine (20:1/0:0). This study provides novel and comprehensive plasma lipidomic signatures of AD patients, identifies lysophosphatidylcholines as excellent potential biomarkers, and would be beneficial to the pathogenetic study, risk assessment and timely diagnosis and treatment of AD.

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