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1.
Neural Regen Res ; 18(1): 141-149, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799534

RESUMO

Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

2.
Sci Total Environ ; 857(Pt 2): 159257, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36208737

RESUMO

Release of toxic cyanobacterial secondary metabolites threatens biosecurity, foodwebs and public health. Microcystis aeruginosa (Ma), the dominant species in global freshwater cyanobacterial blooms, produces exudates (MaE) that cause adverse outcomes including nerve damage. Previously, we identified > 300 chemicals in MaE. It is critical to investigate neurotoxicity mechanisms of active substances among this suite of Ma compounds. Here, we screened 103 neurotoxicity assays from the ToxCast database to reveal targets of action of MaE using machine learning. We then built a potential Adverse Outcome Pathway (AOP) to identify neurotoxicity mechanisms of MaE as well as key targets. Finally, we selected potential neurotoxins matched with those targets using molecular docking. We found 38 targets that were inhibited and eight targets that were activated, collectively mainly related to neurotransmission (i.e. cholinergic, dopaminergic and serotonergic neurotransmitter systems). The potential AOP of MaE neurotoxicity could be caused by blocking calcium voltage-gated channel (CACNA1A), because of antagonizing neurotransmitter receptors, or because of inhibiting solute carrier transporters. We identified nine neurotoxic MaE compounds with high affinity to those targets, including LysoPC(16:0), 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, egonol glucoside, polyoxyethylene (600) monoricinoleate, and phytosphingosine. Our study enhances understanding of neurotoxicity mechanisms and identifies neurotoxins in cyanobacterial bloom exudates, which may help identify priority compounds for cyanobacteria management.


Assuntos
Cianobactérias , Microcystis , Neurotoxinas/toxicidade , Neurotoxinas/metabolismo , Simulação de Acoplamento Molecular , Cianobactérias/química , Microcystis/metabolismo , Exsudatos e Transudatos
3.
Comput Intell Neurosci ; 2022: 7167066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36458233

RESUMO

Background: Application of machine learning (ML) for identification of systemic lupus erythematosus (SLE) has been recently drawing increasing attention, while there is still lack of evidence-based support. Methods: Systematic review and meta-analysis are conducted to evaluate its diagnostic accuracy and application prospect. PubMed, Embase, Cochrane Library, and Web of Science libraries are searched, in combination with manual searching and literature retrospection, for studies regarding machine learning for identifying SLE and neuropsychiatric systemic lupus erythematosus (NPSLE). Quality Assessment of Diagnostic Accuracy Studies (QUADA-2) is applied to assess the quality of included studies. Diagnostic accuracy of the SLE model and NPSLE model is assessed using the bivariate fixed-effect model, and the data are pooled. Summary receiver operator characteristic curve (SROC) is plotted, and area under the curve (AUC) is calculated. Results: Eighteen (18) studies are included, in which ten (10) focused on SLE and eight (8) on NPSLE. The AUC of SLE identification is 0.95, the sensitivity is 0.90, the specificity is 0.89, the PLR is 8.4, the NLR is 0.12, and the DOR is 73. AUC of NPSLE identification is 0.89, the sensitivity is 0.83, the specificity is 0.83, the PLR is 5.0, the NLR is 0.20, and the DOR is 25. Conclusion: Machine learning presented remarkable performance in identification of SLE and NPSLE. Based on the convenience for inclusion factor collection and non-invasiveness of detection, machine learning is expected to be widely applied in clinical practice to assist medical decision making.


Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Aprendizado de Máquina , Área Sob a Curva
4.
Antiviral Res ; : 105478, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464077

RESUMO

SARS-CoV-2 is a betacoronavirus with single-stranded positive-sense RNA, which is a serious global threat to human health. Understanding the molecular mechanism of viral replication is crucial for the development of antiviral drugs. The synthesis of viral polyproteins is a crucial step in viral progression. The synthesis of viral polyproteins in coronaviruses is regulated by the 5'-untranslated region (UTR); however, the detailed regulatory mechanism needs further investigation. The present study demonstrated that the RNA binding protein, RBM24, interacts with the RNA genome of SARS-CoV-2 via its RNA recognition submotifs (RNPs). The findings revealed that RBM24 recognizes and binds to the GUGUG element at stem-loop 4 (SL4) in the 5'-UTR of SARS-CoV-2. The interaction between RBM24 and 5'-UTR prevents 80S ribosome assembly, which in turn inhibits polyproteins translation and the replication of SARS-CoV-2. Notably, other RNA viruses, including SARS-CoV, MERS-CoV, Ebolavirus, rhinovirus, West Nile virus, Zika virus, Japanese encephalitis virus, yellow fever virus, hepatitis C virus, and human immunodeficiency virus-1 also contain one or several G(U/C/A)GUG sequences in the 5'-UTR, which is also targeted by RBM24. In conclusion, the present study demonstrated that RBM24 functions by interacting with the 5'-UTR of SARS-CoV-2 RNA, and elucidated that RBM24 could be a host restriction factor for SARS-CoV-2 and other RNA viruses.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36464270

RESUMO

This work aim to investigate the effects and mechanism of emodin in treating diabetic gastroenteropathy and colonic dysmotility in STZ+HS/HF diet induced diabetic gastroenteropathy rats. Diabetic colonic dysmotility model was established by high-fat /high-glucose (HS/HF) feeding combined with streptozotocin (STZ). Emodin was divided into high, medium and low dose groups. After eight weeks of intervention, fasting blood glucose (FBG) and body weight were measured. Gastrointestinal transmission time was evaluated. Serum vasoactive intestinal peptide (VIP) and substance P (SP) were detected. Colonic protein expression of selective autophagy adaptor proteins p62 and beclin1 were detected by immunohistochemistry. Colonic protein expression of beclin1, autophagy related gene 5 (Atg5), C-kit and p62 were detected by Western Blot. After treating with emodin, gastrointestinal transmission rate was improved. The expression of serum SP was increased and serum VIP was decreased. Colonic c-kit and p62 were up-regulated. The expressions of beclin1 and Atg5 were down-regulated. Emodin can improve colonic dysmotility and promote the recovery of colonic motility and intestinal defecation in diabetic rats. It's mechanism may involved with up-regulating the expression of C-kit and P62, down-regulating the expression of Beclin1 and Atg5 in colon, which are associated with colon over-autophagy of ICC.

6.
Front Cardiovasc Med ; 9: 1061586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465467

RESUMO

Background: Kounis syndrome is a hypersensitive coronary artery disease caused by the body's exposure to allergens, which is induced by various drugs and environmental factors. This entity has been described primarily in isolated case reports and case series. We report a case of type III Kounis syndrome caused by cefoperazone-sulbactam. Case presentation: A 79-year-old man who received an infusion of cefoperazone-sulbactam in Respiratory Department of our hospital for recurrent infections. 28 minutes later, he developed skin flushing of the trunk and extremities, soon followed by loss of consciousness and shock. With antianaphylaxis, pressor therapy, and fluid rehydration, the patient was admitted to the ICU for treatment. During which, he experienced recurrent ventricular fibrillation and a progressive increase in troponin I levels. The ECG of the patient showed that the ST segment elevation of lead II, III, avF, and V3R-V5R was 0.10-0.20 MV. An urgent coronary angiography showed an in-stent thrombosis in the middle part of the right coronary artery, occlusion of the distal flow with TIMI grade 0. The diagnosis was type III Kounis syndrome with cardiogenic shock. Despite aggressive treatment, the patient died on day 7 after ICU admission. Conclusion: Kunis syndrome is a life-threatening disease, and therefore allergic reactions in patients with a history of cephalosporin allergy and coronary stent implantation should be considered and treated promptly.

7.
Ann Palliat Med ; 11(11): 3464-3471, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464970

RESUMO

BACKGROUND: Local thermal ablation is a rapidly developing minimally invasive treatment for lung tumors. This technique has the advantages of less trauma, ease and convenience of the operation, fast recovery, and fewer complications. Thoracic paravertebral block (TPVB) has been demonstrated can provide sufficient pain relief with high safety. This study aimed to evaluate the efficacy of TPVB for anesthesia management during the ablation surgery of lung tumors. METHODS: In our study, a total of 30 patients undergoing Local thermal ablation surgery were enrolled. All patients received TPVB anesthesia before CT positioning starting. Analgesics and rescue drugs were used according to the patient's condition during operation. The main observation and assessment outcome were intraoperative and postoperative Visual Analog Scale (VAS) score. Other outcomes were total dose of analgesics and rescue drugs, incidences of adverse events, and the patients' and surgeons' satisfaction degrees. RESULTS: All patients successfully received ablation surgery under TPVB anesthesia. None of the patients were switched to general anesthesia. There were no statistically differences were found between the preoperative VAS score (0.54±1.12) and the intraoperative VAS score (0.58±1.15) (P>0.05). No adverse events occurred and no rescue drugs were used during operation. The satisfaction scale of both patients and surgeons was 3 points or above, and all patients were discharged from the hospital. CONCLUSIONS: TPVB is an effective and safe anesthesia management technique which can provided adequate pain relief in local thermal ablation therapy for lung tumors. This discovery could provide a better anesthesia protocol for anesthetists in lung tumors ablation surgery, especially when patients have a poor cardiopulmonary function and combined with serious underlying diseases.


Assuntos
Bloqueio Nervoso , Humanos , Estudos Prospectivos , Analgésicos/uso terapêutico , Ultrassonografia de Intervenção , Dor
8.
Brain ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346149

RESUMO

Understanding how variations in the plasma and brain proteome contribute to multiple sclerosis susceptibility can provide important insights to guide drug repurposing and therapeutic development for multiple sclerosis. However, the role of genetically predicted protein abundance in multiple sclerosis remains largely unknown. Integrating plasma proteomics (n = 3,301) and brain proteomics (n = 376 discovery; n = 152 replication) into multiple sclerosis genome-wide association studies (n = 14,802 cases and 26,703 controls), we employed summary-based methods to identify candidate proteins involved in multiple sclerosis susceptibility. Next, we evaluated associations of the corresponding genes with multiple sclerosis at tissue-level using large gene expression quantitative trait data from whole-blood (n = 31,684) and brain (n = 1,194) tissue. Further, to assess transcriptional profiles for candidate proteins at cell-level, we examined gene expression patterns in immune cell types (dataset 1: n = 73 cases and 97 controls; dataset 2: n = 31 cases and 31 controls) for identified plasma proteins, and in brain cell types (dataset 1: n = 4 cases and 5 controls; dataset 2: n = 5 cases and 3 controls) for identified brain proteins. In a longitudinal multiple sclerosis cohort (n = 203 cases followed up to 15 years), we also assessed the corresponding gene-level associations with the outcome of disability worsening. We identified 39 novel proteins associated with multiple sclerosis risk. Based on five identified plasma proteins, four available corresponding gene candidates showed consistent associations with multiple sclerosis risk in whole-blood, and we found TAPBPL upregulation in multiple sclerosis B cells, CD8+ T cells and natural killer cells compared to controls. Among the 34 candidate brain proteins, 18 were replicated in a smaller cohort and 14 of 21 available corresponding gene candidates also showed consistent associations with multiple sclerosis risk in brain tissue. In cell-specific analysis, six identified brain candidates showed consistent differential gene expression in neuron and oligodendrocyte cell clusters. Based on the 39 protein-coding genes, we found 23 genes that were associated with disability worsening in multiple sclerosis cases. The findings present a set of candidate protein biomarkers for multiple sclerosis, reinforced by high concordance in downstream transcriptomics findings at tissue-level. This study also highlights the heterogeneity of cell-specific transcriptional profiles for the identified proteins, and that numerous candidates were also implicated in disease progression. Together, these findings can serve as an important anchor for future studies of disease mechanisms and therapeutic development.

9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(5): 868-875, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36325785

RESUMO

Ubiquitin-proteasome system (UPS) plays an essential role in eukaryotic protein cycle,the dysregulation of which can lead to tumorigenesis.Increased activities of UPS have been observed in the patients with cancers including leukemia.UPS inhibitors can kill cancer cells by affecting ubiquitin-ligating enzyme E3,deubiquitinase,and protein degradation active sites of UPS.Therefore,UPS inhibitors have emerged as an important therapy for treating hematological malignancies,while they are rarely applied in the treatment of acute myeloid leukemia.This paper summarizes the research progress in the inhibitors affecting the protein ubiquitination at different stages of acute myeloid leukemia,aiming to provide new clues for the clinical treatment of acute myeloid leukemia.


Assuntos
Leucemia Mieloide Aguda , Inibidores de Proteassoma , Humanos , Inibidores de Proteassoma/farmacologia , Inibidores de Proteassoma/uso terapêutico , Ubiquitina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitinação , Leucemia Mieloide Aguda/tratamento farmacológico
10.
Int Arch Allergy Immunol ; : 1-10, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36323228

RESUMO

INTRODUCTION: We investigated the molecular mechanism by which B lymphocytes regulate Th1/Th2 imbalance to participate in the pulmonary fibrosis in hypersensitivity pneumonia induced by pigeon shedding in rats. METHODS: CD19+ rats and CD19- rats were used to construct animal models of fibrotic hypersensitivity pneumonia. DAPT was used to inhibit the Notch signaling pathway. The pathological changes were assessed with HE and Masson staining. Protein level was detected with Western blot. Th1/Th2 ratio was analyzed with flow cytometry. Cytokine levels were measured with ELISA. RESULTS: The pathological changes of pulmonary fibrosis were not obvious in the CD19- rats and after DAPT treatment. Notch signaling pathway proteins, including Notch1, Notch2, Jag1, Jag2, DLL1, and DLL4, in lung tissues of model rats were all significantly upregulated than those in control rats. However, these proteins in CD19- rats were lower in CD19+ rats, suggesting that B cells play a key role in inducing pneumonia. Besides, the Th1/Th2 ratio in the BALF of model rats decreased, which was further reversed by DAPT. However, we found that in CD19- rats, the regulation of the Th1/Th2 ratio by the Notch signaling pathway was lost. CONCLUSION: Deleting B lymphocytes or blocking the Notch pathway both reversed the Th1/Th2 imbalance in fibrotic hypersensitivity pneumonia and inhibited pulmonary fibrosis.

11.
Front Surg ; 9: 998590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329976

RESUMO

Background: To investigate the clinical value of ultrasound (US)-guided intervention for frozen shoulder (FS) in the frozen stage. Methods: This study included 40 patients who had primary FS in the frozen stage and were evaluated by US. These 40 patients have all received conservative treatment elsewhere, and no satisfactory results have been achieved, with no improvement in active and passive movement angles, and no improvement in scores within 3 months. Therefore, their previous treatment was set as comparison. All patients underwent US-guided shoulder joint capsule distension by injection of sterilized water. Of these participants, 22 patients with scapulohumeral periarthritis received a compound betamethasone injection, and 14 patients with thickened coracohumeral ligaments (CHLs) underwent acupotomy lysis, and the remaining 4 patients had no extra treatments. The Constant-Murley score (CMS) was evaluated before and after the operation and analysed for each patient. Results: Before treatment, the indices for the thickening of the subaxillary joint capsule, subacromial bursa (with or without effusion), long head of the biceps brachii tendon (LHBBT) and CHL were 40, 22, 16 and 14, respectively. After treatment, all the indices were significantly decreased (all P < 0.010) except for that of the LHBBT (P = 0.123). The patients' CMSs improved, with the median total CMS increasing from 59 points (interquartile range: 53-64 points) to 86 points (interquartile range: 78-90 points) (P < 0.010). While the internal rotation (Ir) of the shoulder joint did not improve (FDRs < 0.50), abduction, forward flexion (Ff) and external rotation (Er) improved significantly (all FDRs = 1.00). Conclusion: Compared with conservative treatment, US-guided intervention for FS in the frozen stage is highly effective and of great clinical value.

12.
Mol Genet Genomic Med ; : e2100, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36370055

RESUMO

BACKGROUND: Nance-Horan syndrome (NHS) is a rare and often overlooked X-linked dominant disorder characterized by dense congenital cataracts, dental abnormalities, and mental retardation. The majority of NHS variations include frameshift mutations, nonsense mutations, microdeletions, and insertions. METHODS: Copy number variation sequencing was performed to determine the microdeletion. The expression of NHS was detected by RT-PCR. Four family members were tested for X chromosome inactivation. RESULTS: In this study, all members were examined for systemic examinations and genetic testing of four members and two affected subjects are observed. We identified a heterozygous microdeletion of -0.52 Mb at Xp22.13 in a female proband presenting NHS phenotypically. The microdeletion contains the REPS2 and NHS genes and was inherited from a phenotypically normal mother. Of interest, the expression NHS of proband was reduced and the skewed X chromosome inactivation rate reached more than 85% compared with her mother and the control. It was concluded that the haploinsufficiency of the NHS gene may account for the majority of clinical symptoms in the affected subjects. The variability among female carriers presumably results from nonrandom X chromosome inactivation. CONCLUSION: Our findings broaden the spectrum of NHS mutations and provide molecular insight into NHS clinical prenatal genetic diagnosis.

13.
World J Diabetes ; 13(11): 986-1000, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36437866

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is the driving force of blindness in patients with type 2 diabetes mellitus (T2DM). DR has a high prevalence and lacks effective therapeutic strategies, underscoring the need for early prevention and treatment. Yunnan province, located in the southwest plateau of China, has a high pre-valence of DR and an underdeveloped economy. AIM: To build a clinical prediction model that will enable early prevention and treatment of DR. METHODS: In this cross-sectional study, 1654 Han population with T2DM were divided into groups without (n = 826) and with DR (n = 828) based on fundus photography. The DR group was further subdivided into non-proliferative DR (n = 403) and proliferative DR (n = 425) groups. A univariate analysis and logistic regression analysis were conducted and a clinical decision tree model was constructed. RESULTS: Diabetes duration ≥ 10 years, female sex, standing- or supine systolic blood pressure (SBP) ≥ 140 mmHg, and cholesterol ≥ 6.22 mmol/L were risk factors for DR in logistic regression analysis (odds ratio = 2.118, 1.520, 1.417, 1.881, and 1.591, respectively). A greater severity of chronic kidney disease (CKD) or hemoglobin A 1c increased the risk of DR in patients with T2DM. In the decision tree model, diabetes duration was the primary risk factor affecting the occurrence of DR in patients with T2DM, followed by CKD stage, supine SBP, standing SBP, and body mass index (BMI). DR classification outcomes were obtained by evaluating standing SBP or BMI according to the CKD stage for diabetes duration < 10 years and by evaluating CKD stage according to the supine SBP for diabetes duration ≥ 10 years. CONCLUSION: Based on the simple and intuitive decision tree model constructed in this study, DR classification outcomes were easily obtained by evaluating diabetes duration, CKD stage, supine or standing SBP, and BMI.

14.
Front Chem ; 10: 1044931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405326

RESUMO

Photothermal treatment is an effective and precise bacterial disinfection method that can reduce the occurrence of bacterial drug resistance. However, most conventional photothermal treatment strategies have the problem that the photothermal response range does not match the infection area. Herein, a metal-organic framework (MOF) nanocomposite responding to the oxidation state of the bacterial infection microenvironment was constructed for near-infrared (NIR) photothermal bacterial inactivation. In this strategy, the MOF was used as a nanocarrier to load tetramethylbenzidine (TMB) and horseradish peroxidase (HPR). The high oxidation state of the bacterial infection microenvironment can trigger the enzyme-catalyzed reaction of the nanocomposite, thereby generating oxidation products with the NIR photothermal effect for bacterial disinfection. The synthesis and characterization of the nanocomposite, oxidation state (H2O2) response effect, photothermal properties, and antibacterial activities were systematically studied. This study provides a new idea for building a precision treatment system for bacterial infection.

15.
Front Microbiol ; 13: 1052533, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406418

RESUMO

Porcine circovirus 4 (PCV4) was identified in 2019 as a novel circovirus species and then proved to be pathogenic to piglets. However, there is a lack of its prevalence in the Southwest of China. To investigate whether PCV4 DNA existed in the Southwest of China, 374 samples were collected from diseased pigs during 2021-2022 and detected by a real-time PCR assay. The results showed that the positive rate of PCV4 was 1.34% (5/374) at sample level, and PCV4 was detected in two of 12 cities, demonstrating that PCV4 could be detected in pig farms in the Southwest of China, but its prevalence was low. Furthermore, one PCV4 strain (SC-GA2022ABTC) was sequenced in this study and shared a high identity (98.1-99.7%) with reference strains at the genome level. Combining genetic evolution analysis with amino acid sequence analysis, three genotypes PCV4a, PCV4b, and PCV4c were temporarily identified, and the SC-GA2022ABTC strain belonged to PCV4c with a specific amino acid pattern (239V for Rep protein, 27N, 28R, and 212M for Cap protein). Phylogenetic tree and amino acid alignment showed that PCV4 had an ancient ancestor with mink circovirus. In conclusion, the present study was the first to report the discovery and the evolutionary analysis of the PCV4 genome in pig herds of the Southwest of China and provide insight into the molecular epidemiology of PCV4.

16.
Front Cardiovasc Med ; 9: 995275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407434

RESUMO

Background: Ventricular septal rupture (VSR) is a type of cardiac rupture, usually complicated by acute myocardial infarction (AMI), with a high mortality rate and often poor prognosis. The aim of our study was to investigate the factors influencing the long-term prognosis of patients with VSR from different aspects, comparing the evaluation performance of the Gensini score, Sequential Organ Failure Assessment (SOFA) score and European Heart Surgery Risk Assessment System II (EuroSCORE II) score systems. Methods: This study retrospectively enrolled 188 patients with VSR between Dec 9, 2011 and Nov 21, 2021at the First Affiliated Hospital of Zhengzhou University. All patients were followed up until Jan 27, 2022 for clinical data, angiographic characteristics, echocardiogram outcomes, intraoperative, postoperative characteristics and major adverse cardiac events (MACEs) (30-day mortality, cardiac readmission). Cox proportional hazard regression analysis was used to explore the predictors of long-term mortality. Results: The median age of 188 VSR patients was 66.2 ± 9.1 years and 97 (51.6%) were males, and there were 103 (54.8%) patients in the medication group, 34 (18.1%) patients in the percutaneous transcatheter closure (TCC) group, and 51 (27.1%) patients in the surgical repair group. The average follow-up time was 857.4 days. The long-term mortality of the medically managed group, the percutaneous TCC group, and the surgical repair group was 94.2, 32.4, and 35.3%, respectively. Whether combined with cardiogenic shock (OR 0.023, 95% CI 0.001-0.054, P = 0.019), NT-pro BNP level (OR 0.027, 95% CI 0.002-0.34, P = 0.005), EuroSCORE II (OR 0.530, 95% CI 0.305-0.918, P = 0.024) and therapy group (OR 3.518, 95% CI 1.079-11.463, P = 0.037) were independently associated with long-term mortality in patients with VSR, and this seems to be independent of the therapy group. The mortality rate of surgical repair after 2 weeks of VSR was much lower than within 2 weeks (P = 0.025). The cut-off point of EuroSCORE II was determined to be 14, and there were statistically significant differences between the EuroSCORE II < 14 group and EuroSCORE II≥14 group (HR = 0.2596, 95%CI: 0.1800-0.3744, Logrank P < 0.001). Conclusion: Patients with AMI combined with VSR have a poor prognosis if not treated surgically, surgical repair after 2 weeks of VSR is a better time. In addition, EuroSCORE II can be used as a scoring system to assess the prognosis of patients with VSR.

17.
Front Psychol ; 13: 984775, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389465

RESUMO

To advertise or estimate demand, many pre-order items appear on crowdfunding platforms. Few studies have explored backers' preferences between crowdfunding projects and pre-order items. To analyze backers' preferences, 1,800 technology and innovation campaigns were collected from the Indiegogo crowdfunding platform. Using the product stage badge, the campaigns in the concept and prototype stages were treated as crowdfunding projects, while those in the production and shipping stages were labeled pre-order items, resulting in 1,305 crowdfunding projects and 495 pre-order items, respectively. Propensity score matching was leveraged to investigate differences in fundraising outcomes between crowdfunding projects and pre-order items. The results indicate that pre-order items have better fundraising outcomes than crowdfunding projects, suggesting that backers are risk-averse on the crowdfunding platform.

18.
J Oncol ; 2022: 4607715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36397762

RESUMO

Purpose: This study aimed to examine the role of chordin-like 2 (CHRDL2) in gastric cancer. Methods: The Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets were screened and the differentially expressed gene CHRDL2 was identified. The CHRDL2 expression was examined in the Human Protein Atlas and TCGA. Clinical data on gastric cancer were evaluated for their association with CHRDL2 by using TCGA and KM-plotter databases. The possible relationship amongst CHRDL2, immune cells, and related genes was investigated via the TIMER database. Enrichment analysis was performed using GO and KEGG pathways to explore the mechanisms. Results: Screening of databases revealed that CHRDL2 was a differentially expressed gene. An increase in cytoplasmic CHRDL2 expression was found in cancer tissues compared with the surrounding normal tissues. The data, together with those from TCGA and the KM-plotter databases, showed that patients with gastric cancer with high level of CHRDL2 have worse prognosis than those with low expression. A strong correlation was found between CHRDL2 expression and T stage, race, pathological grade, and pathological type according to clinical data analysis. CHRDL2 expression is linked to immune infiltration, as shown by the TIMER database. The data suggested that CHRDL2 plays a pivotal role in the tumor microenvironment of gastric cancer and might help tumor cells evade the immune system. Gene set enrichment analysis showed that CHRDL2 is involved in the chemokine signaling route, the intestinal immune network, the MAPK pathway, cell cycle, and the PI3K-Akt signaling system that are associated with the pathological processes of gastric cancer. Conclusion: Patients with gastric cancer with decreased CHRDL2 levels have dramatically improved OS, PFS, and PPS. CHRDL2 plays a pivotal role in enabling tumor cell immune evasion in tumor microenvironment, suggesting a function of this gene in the development of gastric cancer and its immune infiltration. Interfering with CHRDL2 may slow down the development of this malignancy by affecting cell cycle and apoptosis pathways.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36446007

RESUMO

Accurate neonatal brain MRI segmentation is valuable for investigating brain growth patterns and tracking the progression of neurodevelopmental disorders. However, it is a challenging task to use intensity-based methods to segment neonatal brain structures because of small contrast differences between brain regions caused by the inherent myelination process. Although convolutional neural networks offer the potential to segment brain structures in an intensity-independent manner, they suffer from lack of in-plane long-range dependency which is essential for the segmentation. To solve this problem, we propose a novel Transformer-Weighted network (TW-Net) to incorporate in-plane long-range dependency information. TW-Net employs a conventional encoder-decoder architecture with a Transformer module in the middle. The Transformer module uses a rotate-and-flip layer to better calculate the similarity between two patches in a slice to leverage similar patterns of geometrical and texture features within brain structures. In addition, a deep supervision module and squeeze-and-excitation blocks are introduced to incorporate boundary information of brain structures. Compared with state-of-the-art deep learning algorithms, TW-Net outperforms these methods for multiple-label tasks in 2D and 2.5D configurations on two independent public datasets, demonstrating that TW-Net is a promising method for neonatal brain MRI segmentation.

20.
Medicine (Baltimore) ; 101(45): e31388, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397451

RESUMO

OBJECTIVE: This study is conducted to evaluate the efficacy and safety of using multifunctional intubation laryngeal masks with normal frequency jet ventilation in airway interventional therapy. METHODS: A total of 200 patients receiving airway interventional therapy were enrolled in this retrospective study and were divided into 2 groups (group M and group P) by doctors in our hospital to compare the effect of different laryngeal masks. Group M used common laryngeal masks and an anesthesia machine for positive pressure ventilation while group P took multifunctional intubation laryngeal masks and used a jet ventilator for normal frequency jet ventilation. The patients' mean arterial pressure, heart rate, arterial oxygen partial pressure (PaO2) and arterial carbon dioxide partial pressure (PaCO2), and the operation time, recovery score and the patients' and doctors' satisfaction levels were compared between the 2 groups. RESULTS: Both groups were hemodynamically stable, and their PaO2 levels were significantly higher before the operation than that during and after the operation (P < .05). Compared with group M, the PaCO2 level of group P was more stable both during and after the operation, and this difference was statistically significant (P < .05). There was no statistically significant difference in terms of the 2 group's operating time, recovery score, and patients' satisfaction levels (P > .05). However, the satisfaction levels of doctors in group P were higher than that in group M, and this difference was statistically significant (P < .05). CONCLUSION: As statistics show, the intraoperative hemodynamics and PaO2 and PaCO2 levels were stable, and patients, surgeons and anesthesia operators were satisfied. Therefore, it is feasible to apply multifunctional intubation laryngeal masks with normal frequency jet ventilation in airway interventional therapy and it is a safe and ideal way to ensure ventilation.


Assuntos
Ventilação em Jatos de Alta Frequência , Máscaras Laríngeas , Humanos , Estudos Retrospectivos , Gasometria , Oxigênio
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