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OBJECTIVE: To investigate the effect of spectacle correction on refractive progression in children with unilateral myopic anisometropia (UMA). METHODS: In this retrospective study, 153 children with UMA (aged 8-12 years) were recruited and classified into an uncorrected (UC) group (n = 47) and a spectacle (SP) group (n = 106). The spherical equivalent refraction (SER) of the myopic eyes ranged from -0.75 to -4.00 D; the SER of the emmetropic eyes ranged from +1.00 to -0.25 D; anisometropia was ≥1.00 D and the follow-up duration was 1 year. Nineteen subjects from the SP group with follow-up records spanning at least 6 months before and after wearing spectacles were selected as a subgroup. Changes in the SER and axial length (AL), the degree of anisometropia and interocular AL differences of the two groups and the subgroup were analysed. RESULTS: During the 1-year follow-up period, AL and SER changes in myopic eyes were significantly greater than those in emmetropic eyes in the UC group (p < 0.001). For the UC group, the degree of anisometropia and AL change increased (all p < 0.001). For the SP group, there were no significant differences in the degree of anisometropia or AL change (all p > 0.05). When comparing the groups, AL elongation of the myopic eyes in the UC group occurred significantly faster than in the SP group (p = 0.02), and AL elongation for the emmetropic eyes in the UC group occurred significantly slower than in the SP group (p = 0.04). For the subgroup, the AL and SER changes in the myopic eyes 6 months before wearing spectacles occurred significantly faster than those after correction (p < 0.001). CONCLUSIONS: Spectacle correction could prevent increased anisometropia in uncorrected children with UMA by slowing myopia progression in the myopic eyes and accelerating the myopic shift in the contralateral eye.
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BACKGROUND: Ultraviolet (UV)-induced fluorescence technology is widely used in dermatology to identify microbial infections. Our clinical observations under an ultraviolet-induced fluorescent dermatoscope (UVFD) showed red fluorescence on the scalps of androgenetic alopecia (AGA) patients. In this study, based on the hypothesis that microbes are induced to emit red fluorescence under UV light, we aimed to explore the microbial disparities between the AGA fluorescent area (AF group) and AGA non-fluorescent area (ANF group). METHODS: Scalp swab samples were collected from 36 AGA patients, including both fluorescent and non-fluorescent areas. The bacterial communities on the scalp were analyzed by 16S rRNA gene sequencing and bioinformatics analysis, as well as through microbial culture methods. RESULTS: Significant variations were observed in microbial evenness, abundance composition, and functional predictions between fluorescent and non-fluorescent areas. Sequencing results highlighted significant differences in Cutibacterium abundance between these areas (34.06% and 21.36%, respectively; p < 0.05). Furthermore, cultured red fluorescent colonies primarily consisted of Cutibacterium spp., Cutibacterium acnes, Staphylococcus epidermidis, and Micrococcus spp. CONCLUSIONS: This is the first study to investigate scalp red fluorescence, highlighting microbial composition variability across different scalp regions. These findings may provide novel insights into the microbiological mechanisms of AGA.
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Alopecia , Raios Ultravioleta , Humanos , Alopecia/microbiologia , Masculino , Adulto , Pessoa de Meia-Idade , Couro Cabeludo/microbiologia , Feminino , Dermoscopia/métodos , Fluorescência , Microbiota , RNA Ribossômico 16S/genética , Bactérias/genética , Bactérias/isolamento & purificaçãoRESUMO
Skeletal muscle is a vital organ that promotes human movement and maintains posture. Accurate assessment of muscle strength is helpful to provide valuable insights for athletes' rehabilitation and strength training. However, traditional techniques rely heavily on the operator's expertise, which may affect the accuracy of the results. In this study, we propose an automated method to evaluate muscle strength using ultrasound and deep learning techniques. B-mode ultrasound data of biceps brachii of multiple athletes at different strength levels were collected and then used to train our deep learning model. To evaluate the effectiveness of this method, this study tested the contraction of the biceps brachii under different force levels. The classification accuracy of this method for grade 4 and grade 6 muscle strength reached 98% and 96%, respectively, and the overall average accuracy was 93% and 87%, respectively. The experimental results confirm that the innovative methods in this paper can accurately and effectively evaluate and classify muscle strength.
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Aprendizado Profundo , Força Muscular , Músculo Esquelético , Ultrassonografia , Humanos , Força Muscular/fisiologia , Ultrassonografia/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Masculino , Adulto Jovem , Adulto , FemininoRESUMO
Autophagy is essential for eliminating aging and organelle damage that maintaining cellular homeostasis. However, the dysfunction of autophagy has been proven in hair loss such as AGA. Despite the crucial role of TRPML channels in regulating autophagy, their specific function in hair growth remains unclarified. To investigate the biological functions and associated molecular mechanisms of TRPMLs in hair growth, Animal experiments were conducted to confirm the function of TRLMLs activation in promoting hair growth. Subsequently, we analyzed molecular mechanisms in human dermal papilla cells (hDPCs) activated by TRPMLs through transcriptome sequencing analysis. MLSA1(a TRPML agonist) promoted hair regeneration and accelerated hair cycle transition in mice. The activation of TRPMLs upregulated calcium signaling inducing hDPCs to secrete hair growth promoting factors and decrease hair growth inhibiting factors. In addition, activation of TRPMLs triggered autophagy and reduced the generation of ROS, thereby delaying the senescence of hDPCs. All these findings suggested that TRPMLs activation could promote hair growth by regulating hDPCs secretion of hair growth-related factors. Moreover, it may play a prominent role in preventing hDPCs from ROS damage induced by H2O2 or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss.
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Autofagia , Cabelo , Animais , Camundongos , Humanos , Autofagia/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Cabelo/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/citologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Derme/citologia , Derme/efeitos dos fármacos , Canais de Potencial de Receptor Transitório/metabolismo , Sinalização do Cálcio/efeitos dos fármacosRESUMO
Pancreatic adenocarcinoma (PAAD) is one of the most hazardous cancers in digestive system, and the prognosis is notoriously bad. Increasing evidences indicate that Laminin Subunit Gamma 2 (LAMC2) is critical for the initiation and the growth of various sorts of human cancers. However, the involved molecular pathways of LAMC2 in PAAD are still poorly understood. In this study, prediction programs and databases were employed to conduct pan-cancer analysis. Multiple variations of human malignancies showed increased LAMC2 expression, which was positively correlated to a poor prognosis in PAAD. Moreover, LAMC2 was positively correlated with the biomarkers of immune cells including CD19, CD163, and NOS2 in PAAD. The lncRNA C5orf66 /PTPRG-AS1- miR-128-3p -LAMC2 axis was identified to be a potential upstream regulatory pathway of LAMC2 in PAAD. Furthermore, LAMC2 upregulation in PAAD was associated with PD-L1 expression, indicating promoting carcinoma immune cell infiltration. Our study elucidated prognostic and immunological values of LAMC2 in PAAD, providing a promise target for PAAD treatment.
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Adenocarcinoma , Carcinoma , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , Adenocarcinoma/genética , Prognóstico , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , LamininaRESUMO
microRNAs (miRNAs) are a class of non-coding, small RNAs that play an important role in diverse biological processes and diseases. By regulating the expression of eukaryotic genes post-transcriptionally in a sequence-specific manner, miRNAs are widely used to design synthetic RNA switches. However, most of the RNA switches are often dependent on the corresponding ligand molecules, whose specificity and concentration would affect the efficiency of synthetic RNA circuits. Here, a fused transcriptional repressor Gal4BD-Rluc based gene-switch system Gal-miR for miRNA visualization and gene regulation is described. By placing a luciferase downstream gene under the control of endogenous miRNA machinery, the Gal-miR system makes the conversion of miRNA-mediated gene silencing into a ratiometric bioluminescent signal, which quantitatively reflected miRNA-206 activity during myogenic differentiation. Moreover, it demonstrates that this gene-switch system can effectively inhibit breast cancer cell viability, migration and invasion under the control of specific miRNAs by replacing the downstream gene with melittin functional gene. The study proposes a powerful modular genetic design for achieving precise control of transgene expression in a miRNA responsive way, as well as visualizing the dynamics of miRNA activity.
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MicroRNAs , MicroRNAs/genética , Regulação da Expressão Gênica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Diferenciação CelularRESUMO
OBJECTIVE: Amiodarone (AM) is a drug commonly used in patients with ventricular arrhythmias. It can damage vascular endothelial cells and easily cause phlebitis. At present, the prevention and treatment of phlebitis induced by the use of AM is not clear due to the lack of corresponding primary research. Isoliquiritigenin (ISL) has an anti-inflammatory effect, but until now, has not been explored much in the field of research in primary care nursing. The purpose of this study is to investigate the efficacy and mechanism of action of ISL in treating phlebitis induced by AM. METHODS: In our study, we used human umbilical vein endothelial cells (HUVECs) that were divided into three groups: the NC group (normal), the AM group (AM 30 µmol/L for 24 h), and the ISL pretreatment group (isoliquiritigenin 10 µmol/L after 1 h of pretreatment with amiodarone for 24 h). We used CCK-8 to detect cell proliferation, cell scratch assay to detect the migration capability of cells, flow cytometry to measure apoptosis, angiogenesis assay to check the total length and total branches of angiogenesis, and PCR and WB to detect the expression of PCNA, casepase-3, and VEGFA. WB was used to detect NF-κBp65 and p-NF-κBp65 expression. RESULTS: Compared with the AM group, the ISL pretreatment promoted cell proliferation and migration, inhibited cell apoptosis, increased the total length and total branches of angiogenesis, and downregulated p-NF-κBp65 expression. CONCLUSION: ISL shows promise in the prevention and treatment of clinical phlebitis and can be used as a potential therapeutic drug to prevent phlebitis.
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Amiodarona , Chalconas , Flebite , Humanos , Células Endoteliais da Veia Umbilical Humana , Amiodarona/toxicidade , Chalconas/farmacologiaRESUMO
The recovery of spent lithium-ion batteries has not only economic value but also ecological benefits. In this paper, molten-salt electrolysis was employed to recover spent LiCoO2 batteries, in which NaCl-Na2CO3 melts were used as the electrolyte, the graphite rod and the mixtures of the spent LiCoO2 cathode and anode were used as the anode and cathode, respectively. During the electrolysis, the LiCoO2 was electrochemically reduced to Co, and Li+ and O2- entered into the molten salt. The O2- was discharged at the anode to generate CO2 and formed Li2CO3. After electrolysis, the cathodic products were separated by magnetic separation to obtain Co and graphite, and Li2CO3 was recovered by water leaching. The recovery efficiencies of Li, Co, and graphite reached 99.3%, 98.1%, and 83.6%, respectively. Overall, this paper provides a simple and efficient electrochemical method for the simultaneous recovery of the cathode and the anode of spent LiCoO2 batteries.
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OBJECTIVES: Pulmonary embolism (PE) is a life-threatening complication that can occur in patients with lung cancer. In this study, we aimed to identify risk factors and examine the clinical characteristics of advanced lung cancer patients with PE. METHODS: We conducted a retrospective review of patients admitted to our two hospitals between January 2020 and June 2022. The case group consisted of patients with lung cancer and PE, and a closely matched control group was included to identify risk factors. Statistical analysis was conducted using R language. RESULTS: A total of 4957 patients were reviewed, and 162 patients (comprising 54 cases and 108 controls) were included in this study. The prevalence of lung cancer with PE in the study population was 1.08%. The majority of patients were male, and the most common histological subtype was adenocarcinoma (67%), followed by squamous cell carcinoma, small cell carcinoma, and poorly differentiated non-small cell lung cancer. The majority of patients had a high performance status (PS) score, with 50% experiencing respiratory failure (mainly hypoxia) and 33% with deep vein thrombosis (DVT). Forty-eight percent of patients were diagnosed with concurrent PE. Further analysis showed that PE was an independent predictor of poor survival, and a PS score of >1 was an independent risk factor for PE in patients with lung cancer. CONCLUSION: Our study provides valuable insights into the epidemiology and prognosis of PE in lung cancer patients and suggests that a poor ECOG PS, which has not been previously reported, is an independent risk factor for PE.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Embolia Pulmonar , Humanos , Masculino , Feminino , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Estudos de Casos e Controles , Carcinoma Pulmonar de Células não Pequenas/complicações , Estudos Transversais , Embolia Pulmonar/diagnóstico , Fatores de Risco , Estudos RetrospectivosRESUMO
Ovarian cancer (OC), is a tumor that poses a serious threat to women's health due to its high mortality rate and bleak prognosis. Pyroptosis, a type of programmed cell death, is important for determining the prognosis of a patient's prognosis for cancer and may represent a novel target for treatment. However, research into how prognosis is impacted by pyroptosis-related genes (PRGs) is poorly understood. In this study, a prognostic model was created using bioinformatic analysis of PRGs in OC. In OC, we discovered 18 pyroptosis regulators that were either up- or down-regulated. By analyzing prognoses, we developed a 9-genes based prognostic model. Each OC patient received a risk score that could be used to categorize them into two subgroups: those with high risk and/or low chance of survival and those with low risk and/or high chance of survival. Functional enrichment and immunoinfiltration analysis indicated that low expression of immune pathways in high-risk group may account for the decrease of survival possibility. In Multivariable cox regression studies, age, clinical stage and the prognostic model were discovered to be independent factors impacting the prognosis for OC. To forecast OC patient survival, a predictive nomogram was developed. Furthermore, we found a correlation between predictive PRGs and clinical stage, indicating that AIM2, CASP3, ZBP1 and CASP8 may play a role in the growth of tumor in OC. After detailed and complete bioinformatics analysis, the lncRNA RP11-186B7.4/hsa-miR-449a/CASP8/AIM2/ZBP1 regulatory axis was identified in OC. Our study may provide a novel approach for prognostic biomarkers and therapeutic targets of OC.
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Neoplasias Ovarianas , RNA Longo não Codificante , Feminino , Humanos , Prognóstico , RNA Longo não Codificante/genética , Piroptose/genética , Neoplasias Ovarianas/genética , ApoptoseRESUMO
BACKGROUND: Mitochondrial RNA polymerase (POLRMT) is essential for the expression of mitochondrial genes. In recent studies, POLRMT expression promoted non-small cell cancer cell proliferation in cell lines and xenografts. The present study investigated the impact of POLRMT expression and function on lung adenocarcinoma (LUAD) patients. METHOD: Multi-omics data (genomics, transcriptomics, and proteomics) from publicly available databases were used to assess the role of POLRMT expression and function in LUAD. These findings were further verified using cancer tissues from clinical samples. RESULTS: POLRMT was over-expressed in LUADs, with mutation frequencies ranging from 1.30% to 5.71%. Over-expression of POLRMT was associated with an abnormal clinicopathological condition resulting in a decreased lifespan. Furthermore, gene sets enrich analysis revealed that POLRMT expression was linked to WNT/beta-catenin signaling; the expression of downstream target genes was positively correlated with POLRMT expression. Also, POLRMT expression was positively correlated with immunosuppressive genes, thereby affecting immune infiltration. CONCLUSION: POLRMT is over-expressed in LUAD, thereby impacting patient survival. It is also involved in WNT/beta-catenin signaling and may affect tumor infiltration.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/patologia , Via de Sinalização Wnt/genética , RNA Polimerases Dirigidas por DNA/metabolismoRESUMO
DNA-based ancestry inference has long been a research hot spot in forensic science. The differentiation of Han Chinese population, such as the northern-to-southern substructure, would benefit forensic practice. In the present study, we enrolled participants from northern and southern China, each participant was genotyped at â¼400 K single-nucleotide polymorphisms (SNPs) and data of CHB and CHS from 1000 Genomes Project were used to perform genome-wide association analyses. Meanwhile, a new method combining genome-wide association study (GWAS) analyses with k-fold cross-validation in a small sample size was introduced. As a result, one SNP rs17822931 emerged with a p-value of 7.51E - 6. We also simulated a huge dataset to verify whether k-fold cross-validation could reduce the false-negative rate of GWAS. The identified ABCC11 rs17822931 has been reported to have allele frequencies varied with the geographical gradient distribution in humans. We also found a great difference in the allele frequency distributions of rs17822931 among five different cohorts of the Chinese population. In conclusion, our study demonstrated that even small-scale GWAS can also have potential to identify effective loci with implemented k-fold cross-validation method and shed light on the potential maker of rs17822931 in differentiating the north-to-south substructure of the Han Chinese population.
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População do Leste Asiático , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , China , População do Leste Asiático/genética , Frequência do Gene , Genótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Spent lithium-ion batteries (LIBs) and benzene-containing polymers (BCPs) are two major pollutants that cause serious environmental burdens. Herein, spent LIBs and BCPs are copyrolyzed in a sealed reactor to generate Li2CO3, metals, and/or metal oxides without emitting toxic benzene-based gases. The use of a closed reactor allows the sufficient reduction reaction between the BCP-derived polycyclic aromatic hydrocarbon (PAH) gases and lithium transition metal oxides, achieving the Li recovery efficiencies of 98.3, 99.9, and 97.5% for LiCoO2, LiMn2O4, and LiNi0.6Co0.2Mn0.2O2, respectively. More importantly, the thermal decomposition of PAHs (e.g., phenol and benzene) is further catalyzed by the in situ generated Co, Ni, and MnO2 particles, which forms metal/carbon composites and thus prevent the emissions of toxic gases. Overall, the copyrolysis in a closed system paves a green way to synergistically recycle spent LIBs and handle waste BCPs.
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Benzeno , Lítio , Plásticos , Compostos de Manganês , Óxidos , Metais , Fontes de Energia Elétrica , Reciclagem , PolímerosRESUMO
Precise characterization of miRNA expression patterns is critical to exploit the complexity of miRNA regulation in biology. Herein, we developed a Pumilio/FBF (PUF) protein-based engineering luciferase reporter system, PUF/miR, to quantitatively and non-invasively sense miRNA activity in living cells and animal models. We verified the feasibility of this reporter by monitoring the expression of several types of miRNAs (miRNA-9, 124a, 1, and 133a) in neural and muscle differentiated cells as well as subcutaneous or tibial anterior muscles in mice. The quantitative RT-PCR also validated the reliability and quantitative consistency of bioluminescence imaging in detecting miRNA expression. We further effectively employed this reporter system to visualize the expression of miRNA-1 and miRNA-133a in mouse models of skeletal muscle injury. As a non-invasive and convenient innovative approach, our results have realized the positive bioluminescence imaging of endogenous miRNAs in vitro and in vivo using the PUF/miR system. We believe that this approach would provide a potential means for noninvasive monitoring of disease-related miRNAs and could facilitate a deeper understanding of miRNA biology.
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MicroRNAs , Camundongos , Animais , Reprodutibilidade dos Testes , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular , Luciferases/genética , Diagnóstico por ImagemRESUMO
Transient receptor potential vanilloid 1 (TRPV1) ion channel is a classic analgesic target, but antagonists of TRPV1 failed in clinical trials due to their side effects like hyperthermia. Here we rationally engineer a peptide s-RhTx as a positive allosteric modulator (PAM) of TRPV1. Patch-clamp recordings demonstrate s-RhTx selectively potentiated TRPV1 activation. s-RhTx also slows down capsaicin-induced desensitization of TRPV1 in the presence of calcium to cause more calcium influx in TRPV1-expressing cells. In addition, our thermodynamic mutant cycle analysis shows that E652 in TRPV1 outer pore specifically interacts with R12 and K22 in s-RhTx. Furthermore, we demonstrate in vivo that s-RhTx exhibits long-lasting analgesic effects in noxious heat hyperalgesia and CFA-induced chronic inflammatory pain by promoting the reversible degeneration of intra-epidermal nerve fiber (IENF) expressing TRPV1 channels in mice, while their body temperature remains unaffected. Our results suggest s-RhTx is an analgesic agent as a PAM of TRPV1.
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Analgesia , Canais de Potencial de Receptor Transitório , Camundongos , Animais , Cálcio , Canais de Cátion TRPV/genética , Dor/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Capsaicina/farmacologia , Peptídeos/farmacologia , Peptídeos/uso terapêuticoRESUMO
BACKGROUND: Klebsiella pneumoniae is a major pathogen of bacterial liver abscess in Asia. Particularly, patients with community-acquired Klebsiella pneumoniae liver abscess (CA-KPLA) tend to have a higher risk of invasive infection and pulmonary is a common invasive infectious site, making it a global clinical crisis. Therefore, considerable attention should be focused on the early prediction and active treatment strategies of such patients. METHODS: The clinical data of 127 CA-KPLA cases hospitalized from January 2017 to February 2022 were collected from a single center. Risk factors were analyzed by the use of univariable and multivariable analysis. Furthermore, independent risk factors of pulmonary affection were utilized to construct a predictive nomogram. RESULTS: The incidence of pulmonary affection in KPLA patients was 57.5% (73/127) and the majority manifested as nodular lesions with cavities and pleural effusion in chest CT images. Based on the predictive nomogram, the SOFA score (>2) was defined as the most dominant independent risk factor for the occurrence of pulmonary affection, followed by the maximum diameter of liver abscess (>3 cm), multiple liver abscesses, bacteremia, and badly-controlled diabetes sequentially. The validation of this nomogram also demonstrated good discriminative ability and satisfactory consistency. Finally, early drainage of liver abscess, initial combinational antibiotics, and early Carbapenem-including antibiotic usage were established as favorable factors for therapy in pulmonary affected CA-KPLA patients. CONCLUSION: This study provided an effective model for the early prediction of pulmonary affection in patients with CA-KPLA and some rational strategies for their early therapeutic remission.
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Infecções Comunitárias Adquiridas , Infecções por Klebsiella , Abscesso Hepático Piogênico , Pneumonia , Humanos , Klebsiella pneumoniae , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella , Abscesso Hepático Piogênico/epidemiologia , Abscesso Hepático Piogênico/tratamento farmacológico , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia/tratamento farmacológicoRESUMO
Background: An evaluation system is urgently needed to describe early predictors of the outcome of high-flow nasal cannula (HFNC) oxygen therapy in acute hypoxemic respiratory failure (AHRF) patients. Methods: All consecutive AHRF patients in a Respiratory Intensive Care Unit (RICU) receiving HFNC therapy between January 2019 and December 2021 were enrolled. Results: Of the 106 enrolled AHRF subjects, 57 (53.8%) succeeded in HFNC therapy and 49 (46.2%) failed. Being male (p = 0.006), initial respiratory rate oxygenation (ROX) index (p = 0.011), Acute Physiology and Chronic Health Evaluation II score (p = 0.007) and 24-h ROX index variation rate (p = 0.004) were independent factors of HFNC outcome; among these, 24-h ROX index variation rate (area under the curve = 0.825) was the best evaluation indicator. Conclusion: 24-h ROX index variation rate, introduced by our study, has shown the best potential to predict HFNC outcome in AHRF patients.
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Cânula , Insuficiência Respiratória , Humanos , Masculino , Feminino , Taxa Respiratória , Insuficiência Respiratória/terapia , Oxigenoterapia , Unidades de Terapia Intensiva , Oxigênio/uso terapêuticoRESUMO
As a strategy that induces gene silencing by the delivery of small interfering RNA (siRNA) targeting a specific gene locus into cells or tissues, RNA interference (RNAi) technology holds the potential to be a powerful tool in a range of intractable disorder therapeutics. However, reliable noninvasive probes for visualizing the siRNA delivery and silencing efficiency have become a major obstacle in siRNA-based treatment. Here, we describe the development of an RNA-binding protein Pumilio/FBF (PUF)-based reporter probe for the monitoring of siRNA delivery efficiency and functional screening of effective siRNA target sites in vivo. This reporter consisted of a Firefly luciferase (Fluc) gene whose expression is regulated by the unique interaction architecture of the PUF protein with its Nanos response element (NRE) target RNA. We showed that a robust and rapid increase in the luminescence signal was detected by the successful delivery of siRNA against the enhanced green fluorescent protein (EGFP) or p53 genes into mammalian cells or the livers of mice. The delivery efficiencies of various commercial transfection vehicles were quantitatively evaluated with this reporter. In addition, we also employed in vivo bioluminescence imaging to screen and identify the most potent siRNA targeting p53. Our study indicates that the positive-readout reporter represents a promising indicator for siRNA optimization and visualization, advancing the development of siRNA therapeutic products.
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Inativação Gênica , Mamíferos , Camundongos , Animais , Interferência de RNA , RNA Interferente Pequeno/genética , Genes Reporter/genética , TransfecçãoRESUMO
Objective: Non-small cell lung cancer (NSCLC) explains about 80 percent of whole lung cancers, and its 5-year survival rate is impoverished, as when people are first diagnosed, 68% of whom are identified at a dangerous stage. The molecular mechanisms of NSCLC are still being explored. Methods: GSE18842 and GSE19804 were exerted to scan for diversely expressed genes (DEGs) in NSCLC, and then we used GEPIA for the validation of DEGs expression. The prognostic values were determined through Kaplan-Meier analysis. Three target prediction databases indicated potential microRNAs (miRNAs), while miRNet predicted hsa-miR-1-3p's upstream long non-coding RNAs (lncRNAs) and pseudogenes. UALCAN was utilized to identify the co-expressed genes of PAICS, while enrichment analysis on them was managed with Enrichr. Results: We initially found that the gene expression level of cyclin B1 (CCNB1), cyclin-dependent kinases1 (CDK1), and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) had a notable increase in NSCLC. We predicted 6, 10, and 7 microRNAs to target CCNB1, CDK1, and PAICS, respectively. Among miRNA-mRNA (microRNA-messenger RNA) pairs, we deduced that the hsa-miR-1-PAICS axis was the most potential one to inhibit the occurrence of NSCLC. We also noted that the hsa-miR-1-3p-PAICS axis participated in regulating the process of mitosis with mechanical functions. Moreover, we identified 5 pseudogenes and 33 long non-coding RNAs (lncRNAs) that might inhibit the hsa-miR-1-3p-PAICS axis in NSCLC. Conclusions: The pseudogene/lncRNA-hsa-miR-1-3p-PAICS is very important in NSCLC on the basis of this study, thus providing us with effective treatments and promising biomarkers for the diagnosis of NSCLC.
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Photoacoustic (PA) imaging technology is of some value in medical diagnoses such as breast cancer detection, vasculature imaging, and surgery navigating. While as most imaging objects are bounded, the received RF signals consist of the direct-arrived signals (DAS) from the PA sources and the boundary-reflected signals (BRS). The undesired BRS will severely impair the quality during the image reconstruction. They will bring in many artifacts and confuse the actual shape and location of the PA sources. We improved the reconstruction procedure by removing the BRS before the regular reconstruction process to suppress those artifacts. To verify our proposed method, we compared the results of the conventional and optimized procedures experimentally. In terms of qualitative observation, the reconstructed images by the optimized procedure illustrate fewer artifacts and more accurate shapes of the PA sources. To quantitatively evaluate the traditional and the optimized imaging procedure, we calculated the Distribution Relative Error (DRE) between each experiment result and its standard drawing of the phantoms. For both phantoms and the ex-vivo sample, the DREs of reconstruction result by the optimized reconstruction procedure decrease significantly. The results suggest that the optimized reconstruction process can effectively suppress the reflection artifacts and improve the shape accuracy of the PA sources.