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Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).
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Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder characterized by coexisting reproductive dysfunction and glucolipid metabolic disturbance, affecting 8%-13% of women of reproductive age and 3%-11% of adolescent females. Due to the highly heterogeneous clinical features, symptom-oriented individualized strategies are commonly adopted for the treatment of PCOS. Chronic low-grade inflammation is one of the core mechanisms for the occurrence of PCOS. Macrophages, as foundational cells of innate immunity, play an indispensable role in modulating systemic inflammatory responses. The imbalance of macrophage M1/M2 polarization is involved in chronic low-grade inflammation in PCOS via pathways such as activating pro-inflammatory responses, disrupting ovarian tissue repair, stimulating excessive synthesis of androgens, and promoting the occurrence of insulin resistance. Reshaping the phenotype of macrophages might serve as a potential therapeutic strategy for PCOS. Traditional Chinese medicine (TCM) holds that spleen deficiency and phlegm dampness is a crucial pathogenesis of PCOS. The spleen, being in charge of defensive function, plays a key role in ensuring normal physiological functions such as transportation and defense against external pathogen during the occurrence and development of PCOS. The imbalance of macrophage polarization resembles the transition from spleen being in charge of defensive function to spleen losing its defensive role in TCM. Therefore, this paper, for the first time, explores the deep connection between macrophage polarization and the pathogenesis of chronic low-grade inflammation in PCOS from the TCM theory of spleen being in charge of defensive function, providing theoretical support and new research directions for the treatment and drug research of PCOS.
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In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl2 was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L-1 CoCl2 for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.
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Objective To improve the fixation method of the transmission electron microscope for better morphological preservation of mitochondria and lipid droplets in mouse brown adipose tissue. Methods The fixation method for mouse brown adipose tissue was optimized, mainly including an increased concentration of paraformaldehyde from 2% to 4% in the pre-fixative, employment of transcardial perfusion followed by immersion fixation in pre-fixation, and using imidazole-buffered osmium tetroxide as the post-fixative. The ultrastructures of brown adipocytes prepared by the improved method were observed and compared with those of a known standard protocol (3 mice in each group). The improved method was further validated in the quantitative analysis of mitochondrial cristae density and lipid droplets. Results The mitochondrial cristae and membrane structure of other organelles of brown adipocytes were better preserved using the optimized method compared with those of the standard method. Lipid droplets were presented as round structures with high electron density instead of vacuolated appearances. Using this method, we observed that the density of mitochondrial cristae and the content of lipid droplets increased in brown adipocytes after cold adaptation. Conclusion The optimized method can better preserve the ultrastructure of organelles in brown adipocytes, especially mitochondria and lipid droplets, and ma)' be applicable for studying the ultrastructures remodeling of brown adipose tissue under different physiological or pathological conditions.
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Vascular dementia(VD) is a condition of cognitive impairment due to acute and chronic cerebral hypoperfusion. The available therapies for VD mainly focus on mitigating cerebral ischemia, improving cognitive function, and controlling mental behavior. Achievements have been made in the basic and clinical research on the treatment of VD with traditional Chinese medicine(TCM) active components, including Ginkgo leaf extract, puerarin, epimedium, tanshinone, and ginsenoside. Most of these components have anti-inflammatory, anti-apoptotic, anti-oxidant, and neuroprotective effects, and puerarin demonstrates excellent performance in mitigating cholinergic nervous system disorders and improving synaptic plasticity. Puerarin, ginkgetin, and epimedium are all flavonoids, while tanshinone is a diterpenoid. Puerariae Lobatae Radix, pungent in nature, can induce clear Yang to reach the cerebral orifices and has the wind medicine functions of ascending, dispersing, moving, and scurrying. Puerariae Lobatae Radix entering collaterals will dredge blood vessels to promote blood flow, and that entering the sweat pore will open the mind, which is in line with the TCM pathogenesis characteristics of VD. This study reviews the progress in the mechanism of puerarin, the main active component of Puerariae Lobatae Radix, in treating VD. Puerarin can ameliorate cholinergic nervous system disorders, reduce excitotoxicity, anti-inflammation, inhibit apoptosis, alleviate oxidative stress injury, enhance synaptic plasticity, up-regulate neuroprotective factor expression, promote cerebral circulation metabolism, and mitigate Aβ injury. The pathways of action include activating nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE), vascular endothelial growth factor(VEGF), extracellular regulated protein kinases(ERK), phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), Janus-activating kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3), AMP-activated protein kinase(AMPK), as well as inhibiting the tumor necrosis factor α(TNF-α), transient receptor potential melastatin 2(TRPM2)/N-methyl-D-aspartate receptor(NMDAR), p38 mitogen-activated protein kinase(p38 MAPK), Toll-like receptor 4(TLR4)/nuclear factor-kappaB(NF-κB), early growth response 1(Egr-1), and matrix metalloproteinase 9(MMP-9). By reviewing the papers about the treatment of VD by puerarin published by CNKI, Wanfang, VIP, PubMed, and Web of Science in the last 10 years, this study aims to support the treatment and drug development for VD.
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Humanos , Demencia Vascular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , FN-kappa B/metabolismo , Antioxidantes , Isquemia Encefálica , ColinérgicosRESUMEN
Cerebral hemorrhage accounts for about 10%-15% of all strokes, and its pathogenesis is complex. Currently, the main clinical treatment is mainly medical symptomatic treatment, including the use of antihypertensive drugs, hypoglycemic drugs, and hemostatic drugs, and surgical treatment is required in some cases, but there is still a lack of effective treatment. In recent years, traditional Chinese medicine and proprietary Chinese medicine have been widely accepted for their stable efficacy, high safety, and low cost. Rhei Radix et Rhizoma is one of the most commonly used herbal medicines for the treatment of cerebral hemorrhage. This paper summarizes the relevant literature on the treatment of cerebral hemorrhage with Rhei Radix et Rhizoma and finds that its active ingredients are mainly anthraquinones, such as emodin, Rhei Radix et Rhizoma acid, and Rhei Radix et Rhizoma phenol. The herbal formulas are Da Chengqitang, Shengdi Dahuangtang, Liangxue Tongyufang, and Naoxueshu oral liquid. The effects involve protecting the blood-brain barrier, promoting hematoma absorption, reducing inflammation levels, decreasing lactic acid accumulation at the bleeding site, and increasing the expression of brain-derived neurotrophic factors. The pathways involved include aquaporin 4 (AQP4), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase 1/2 (ERK1/2), Toll-like receptor 4 (TLR4), nuclear transcription factor-κB (NF-κB), nuclear factor E2-related factor 2 (Nrf2), and Wnt3a/β-linked protein pathway. This paper summarizes the progress of clinical studies and animal experiments on the treatment of cerebral hemorrhage with active ingredients of Rhei Radix et Rhizoma and herbal compounds containing Rhei Radix et Rhizoma, so as to provide a reference for the treatment protocol of cerebral hemorrhage.
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OBJECTIVE@#To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis.@*METHODS@#Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×102 copies/ml), low load group (>5×102-<5×105 copies/ml) and high load group (≥5×105copies/ml). The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group.@*RESULTS@#The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×109/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups.@*CONCLUSION@#The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.
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Humanos , Niño , Femenino , Linfohistiocitosis Hemofagocítica , Estudios Retrospectivos , Factores de Riesgo , ADN , PronósticoRESUMEN
This study determined the whole genome sequence and phylogenetic characteristics of a rat coronavirus.Nucleic acids were extracted from rat intestinal tissues collected in Inner Mongolia,and high-throughput sequencing was performed.A novel alphacoronavirus was present in the samples.The complete genome was amplified with PCR and RACE.Multiple se-quence alignment and a phylogenetic tree were constructed in MEGA.The whole genome of the rat coronavirus,denoted NMR-13,was 27 674 bp and included two non-coding regions and eight open reading frames,successively 5'UTR-ORF1ab-S-ORF3-E-M-ORF6-N-ORF8-3'UTR.Sequence identity analysis indicated that NMR-13 was most closely related to alphacoronavirus,which shared 91.3%nt identity with strain FiCoV/UMN2020.NMR-13h shared the next highest-sequence identitywiththe strains Lucheng/Lijiang-170,Lucheng/Ruian-83 and Lucheng/Lijiang-71 found in Zhejiang Province,China(79.49%,80.6%and 81.0%,respectively).Phylogeneticanalysis indicated that NMR-13 clustered with FiCoV/UMN2020.Recombination analy-sis indicated no recombination phenomenon.A rat coronavirus was isolated in this study,thus enriching the diversity of known alphacoronaviruses,and providing a reference for understanding the molecular genetic characteristics and molecular evolution of mouse coronaviruses in China.
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Objective To investigate the correlation between isoniazid concentration in plasma and lymph node tissue of patients with lymph node tuberculosis,and to explore its clinical value.Methods The basic information of patients with lymph node tuberculosis in our hospital and venous blood samples and neck lymph node tissue samples at different time points were collected.UPLC-MS/MS method was established and isoniazid concentration in plasma and neck lymph node tissue samples was quantitatively detected,and the correlation between isoniazid concentration in plasma and lymph node tissue was analyzed.Results The linear range of isoniazid blood concentration and lymph node tissue concentration were 0.25-16 μg·mL-1(r=0.999 8)and 2-128 μg·g-1(r=0.998 8),respectively.The precision,accuracy,and matrix effect of each quality control sample met the requirements.Plasma isoniazid concentration and lymph node tissue isoniazid concentration were significantly correlated at 10 min(rs=0.501 1,P=0.001),30 min(rs=0.402 8,P=0.005)and 60 min(rs=0.614 6,P=0.001)after intravenous infusion of isoniazid.The ratio of lymph node tissue isoniazid concentration to plasma isoniazid concentration was 1.46(0.62,3.55)mL·g-1 at 10 min.At 30 min,the ratio was 5.25(4.61,11.61)mL·g-1.At 60 min,the ratio was 6.62(4.42,10.78)mL·g-1.Conclusion The established UPLC-MS/MS method has good specificity,high sensitivity,accurac and precision.Monitoring plasma isoniazid concentration provides a reference for the rational use of isoniazid in patients with lymphatic tuberculosis.
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To investigate the associations between gene polymorphisms of signal transducer and activator of transcription 3 (STAT3) and liver cirrhosis (LC) after hepatitis B virus (HBV) infection. A case-control study was conducted in 243 patients with hepatitis B cirrhosis (HBV-LC, case group) and 486 HBV-infected subjects without LC (non-LC, control group) collected from January 2018 to September 2020 at the Changsha Central Hospital Affiliated to Nanhua University. Three single nucleotide polymorphisms (SNPs) of STAT3 gene, including rs4796793C>G, rs2293152C>G, and rs1053004T>C were selected through literature and biological information database, and the genotypes were detected by real-time fluorescent quantitative PCR (RFQ-PCR). The distribution differences of STAT3 SNPs genotypes between the two groups were compared using Chi-square test and haplotype analysis was conducted by Shesis online. The proportion of HBV C genotype in HBV-LC patients was significantly higher than that in the control group (80.91% vs. 70.79%, χ2=7.109, P=0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 vs. 1.95±0.54, t=3.801, P=0.000). The genotypes distributions of rs4796793, rs2293152, and rs1053004 were not significantly different between HBV-LC and non-LC in overall analysis and stratified analysis by gender (χ²=2.610, 1.505, 0.586, 2.653, 2.685, 1.583, 0.351, 5.388, 0.339, respectively, P>0.05 for each). Among the subjects infected with HBV genotype C, rs1053004 CC (vs. TT) significantly increased the risk of HBV-LC [odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, rs4796793 GG genotype (vs. CC) and G allele (vs. C) significantly increased the risks of HBV-LC (OR = 2.17, 95%CI: 1.11-4.23; OR = 1.45, 95%CI: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of rs4796793, rs2293152, and rs1053004 was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% vs. 35.6%, χ²=9.949, P = 0.001). The correlation between STAT3 and HBV-LC is different in HBV-infected subjects with different infection status. The HBV-infected subjects carrying haplotype rs4796793C-rs2293152G-rs1053004T of STAT3 gene have significantly decreased risk of LC.
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Humanos , Carcinoma Hepatocelular/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple , Factor de Transcripción STAT3/genéticaRESUMEN
OBJECTIVE@#To propose an adaptive weighted CT metal artifact reduce algorithm that combines projection interpolation and physical correction.@*METHODS@#A normalized metal projection interpolation algorithm was used to obtain the initial corrected projection data. A metal physical correction model was then introduced to obtain the physically corrected projection data. To verify the effectiveness of the method, we conducted experiments using simulation data and clinical data. For the simulation data, the quantitative indicators PSNR and SSIM were used for evaluation, while for the clinical data, the resultant images were evaluated by imaging experts to compare the artifact-reducing performance of different methods.@*RESULTS@#For the simulation data, the proposed method improved the PSNR value by at least 0.2 dB and resulted in the highest SSIM value among the methods for comparison. The experiment with the clinical data showed that the imaging experts gave the highest scores of 3.616±0.338 (in a 5-point scale) to the images processed using the proposed method, which had significant better artifact-reducing performance than the other methods (P < 0.001).@*CONCLUSION@#The metal artifact reduction algorithm proposed herein can effectively reduce metal artifacts while preserving the tissue structure information and reducing the generation of new artifacts.
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Algoritmos , Artefactos , Procesamiento de Imagen Asistido por Computador/métodos , Metales , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE@#To build a helical CT projection data restoration model at random low-dose levels.@*METHODS@#We used a noise estimation module to achieve noise estimation and obtained a low-dose projection noise variance map, which was used to guide projection data recovery by the projection data restoration module. A filtering back-projection algorithm (FBP) was finally used to reconstruct the images. The 3D wavelet group residual dense network (3DWGRDN) was adopted to build the network architecture of the noise estimation and projection data restoration module using asymmetric loss and total variational regularization. For validation of the model, 1/10 and 1/15 of normal dose helical CT images were restored using the proposed model and 3 other restoration models (IRLNet, REDCNN and MWResNet), and the results were visually and quantitatively compared.@*RESULTS@#Quantitative comparisons of the restored images showed that the proposed helical CT projection data restoration model increased the structural similarity index by 5.79% to 17.46% compared with the other restoration algorithms (P < 0.05). The image quality scores of the proposed method rated by clinical radiologists ranged from 7.19% to 17.38%, significantly higher than the other restoration algorithms (P < 0.05).@*CONCLUSION@#The proposed method can effectively suppress noises and reduce artifacts in the projection data at different low-dose levels while preserving the integrity of the edges and fine details of the reconstructed CT images.
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Algoritmos , Artefactos , Tomografía Computarizada Espiral , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE@#To propose a nonlocal spectral similarity-induced material decomposition network (NSSD-Net) to reduce the correlation noise in the low-dose spectral CT decomposed images.@*METHODS@#We first built a model-driven iterative decomposition model for dual-energy CT, optimized the objective function solving process using the iterative shrinking threshold algorithm (ISTA), and cast the ISTA decomposition model into the deep learning network. We then developed a novel cost function based on the nonlocal spectral similarity to constrain the training process. To validate the decomposition performance, we established a material decomposition dataset by real patient dual-energy CT data. The NSSD-Net was compared with two traditional model-driven material decomposition methods, one data-based material decomposition method and one data-model coupling-driven material decomposition supervised learning method.@*RESULTS@#The quantitative results showed that compared with the two traditional methods, the NSSD-Net method obtained the highest PNSR values (31.383 and 31.444) and SSIM values (0.970 and 0.963) and the lowest RMSE values (2.901 and 1.633). Compared with the datamodel coupling-driven supervised decomposition method, the NSSD-Net method obtained the highest SSIM values on water and bone decomposed results. The results of subjective image quality assessment by clinical experts showed that the NSSD-Net achieved the highest image quality assessment scores on water and bone basis material (8.625 and 8.250), showing significant differences from the other 4 decomposition methods (P < 0.001).@*CONCLUSION@#The proposed method can achieve high-precision material decomposition and avoid training data quality issues and model unexplainable issues.
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Humanos , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Relación Señal-Ruido , Tomografía Computarizada por Rayos X/métodos , AguaRESUMEN
ObjectiveTo study the virulence and biofilm inhibition effect of Fufang Huangbai Fluid Paint (FFHBFP) on methicillin-resistant Staphylococcus aureus (MRSA), and to explore the antibacterial effect of FFHBFP on MRSA, which provides a theoretical basis and reference for clinical medication. MethodFirstly, the microdilution method and time–growth curve were used to determine the minimum inhibitory concentration (MIC) of FFHBFP and vancomycin (VAN) against MRSA and the effect on bacterial growth. The effects of FFHBFP and VAN on the inhibition of MRSA virulence factor lipase and restoration of hydrogen peroxide (H2O2) sensitivity were detected under sub-minimum inhibitory concentration (sub-MIC). The inhibitory effect of FFHBFP and VAN on MRSA biofilm formation and maturation was detected by the microplate method. The morphological changes of mature biofilms before and after administration were observed under a scanning electron microscope (SEM). Real-time polymerase chain reaction (Real-time PCR) was utilized to detect the effect of 50.600 g·L-1 concentration of FFHBFP on the expression of MRSA virulence gene crtM and biofilm-forming genes fnbA and icaA. Finally, molecular docking technology was used to predict the mechanism of potential antibacterial active ingredients of FFHBFP in inhibiting the virulence and biofilm of MRSA. ResultThe MIC of VAN was 2 mg·L-1, and VAN below 1 mg·L-1 exerted no effect on MRSA growth. The MIC of FFHBFP was not determined, while the 101.200-202.400 g·L-1 original solution inhibited MRSA growth. Compared with the blank group and the VAN group, sub-MIC (25.300-50.600 g·L-1 original solution) inhibited lipase and recovered MRSA sensitivity to H2O2 (P<0.01). The results of the microplate method showed that FFHBFP (25.300-202.400 g·L-1 original solution) inhibited biofilm formation and maturation (P<0.05, P<0.01). The SEM exhibited that FFHBFP made the structure of biofilm loose and the size of the bacteria varied. FFHBFP at 50.600 g·L-1 concentration can inhibit the expression of related virulence genes and biofilm-forming genes (P<0.05, P<0.01), and molecular docking results also showed that the main antibacterial active ingredients in FFHBFP have good binding ability to the target. ConclusionFFHBFP that cannot directly kill MRSA exerts clinical efficacy by impairing virulence expression, biofilm formation, and other pathogenic properties.
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ObjectiveTo explore the potential anti-tuberculosis mechanism of Kanglao granule through network pharmacology. MethodThe active components of Kanglao granule were retrieved from related databases and the potential targets of the components from SwissTargetPrediction. Targets of the tuberculosis were screened from GeneCards and National Center for Biotechnology Information (NCBI), and the anti-tuberculosis targets of the prescription were further identified. STRING and Cytoscape 3.8.0 were employed to construct the Chinese medicinal-disease target-signaling pathway network and screen core targets. Then gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed. Finally, AutoDock Vina was used for molecular docking between the active components of the prescription and key proteins and Western blotting for verifying the interaction between them. ResultA total of 29 important chemical components in the prescription were screened out, including β-sitosterol, sesamin, and kaempferol. A total of 28 key anti-tuberculosis targets were retrieved, such as protein kinase B1 (Akt1), epidermal growth factor receptor (EGFR), hypoxia inducible factor-1A (HIF-1A), proto-oncogene tyrosine-protein kinase (SRC), and matrix metalloproteinase-9 (MMP-9). Bioinformatics analysis showed the 28 targets were involved in 41 GO terms such as oxygen metabolism, nucleic acid transcription, and metabolic enzyme pathway, and 28 key KEGG pathways, including Mycobacterium tuberculosis signaling pathway and phosphatidylinositol 3 kinase/protein kinase B pathway. Molecular docking results showed that Akt1 had the strongest binding affinity to sesamin. In vitro experiment indicated that sesamin inhibited the growth of M. tuberculosis by suppressing the phosphorylation of Akt1. ConclusionKanglao granule improved the sterilization level and immune response through multi-component, multi-target, and multi-pathway interactions, thereby achieving therapeutic effect on tuberculosis. Akt1 is one of the important targets involved in the treatment of tuberculosis.
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Objective: To explore the role of parental reproductive age on the risk of overweight and obesity in offspring. Methods: The participants were derived from physical examination data of students aged 6-18 years in seven provinces in China, and questionnaire survey was used to collect demographic characteristics and lifestyle information of the students and their parents. A total of 41 567 children with complete data were included. According to the restricted cubic spline curve, maternal reproductive age was divided into three categories, 14-23, 24-28, and 29-38 years, and paternal reproductive age was divided into 14-23, 24-30, and 31-42 years. Multivariate logistic regression model was used to analyze the association between parental reproductive age and parental nutritional status and the risk of overweight and obesity in offspring. Results: The mean age of 41 567 children was (10.6±3.2) years, and the mean paternal and maternal age were (27.9±4.4) years and (25.8±4.0) years, respectively. The detection rate of overweight and obesity was 23.4%. After adjusting factors of children diet and behaviors, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 24-28 years was 1.11 (1.04-1.18) and 1.16 (1.08-1.24), respectively. When none parents were overweight and obese, the difference of obesity risk was not statistically significant. When both parents were overweight and obese, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 14-28 years old was 1.27 (1.00-1.62) and 1.33 (1.07-1.65) respectively. Conclusion: Parental reproductive age and parental overweight and obesity status may both increase the risk of overweight and obesity in offspring, with a significant interaction effect.
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Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven , Padre , Madres , Obesidad/epidemiología , Sobrepeso/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVE@#To investigate the performance of different low-dose CT image reconstruction algorithms for detecting intracerebral hemorrhage.@*METHODS@#Low-dose CT imaging simulation was performed on CT images of intracerebral hemorrhage at 30%, 25% and 20% of normal dose level (defined as 100% dose). Seven algorithms were tested to reconstruct low-dose CT images for noise suppression, including filtered back projection algorithm (FBP), penalized weighted least squares-total variation (PWLS-TV), non-local mean filter (NLM), block matching 3D (BM3D), residual encoding-decoding convolutional neural network (REDCNN), the FBP convolutional neural network (FBPConvNet) and image restoration iterative residual convolutional network (IRLNet). A deep learning-based model (CNN-LSTM) was used to detect intracerebral hemorrhage on normal dose CT images and low-dose CT images reconstructed using the 7 algorithms. The performance of different reconstruction algorithms for detecting intracerebral hemorrhage was evaluated by comparing the results between normal dose CT images and low-dose CT images.@*RESULTS@#At different dose levels, the low-dose CT images reconstructed by FBP had accuracies of detecting intracerebral hemorrhage of 82.21%, 74.61% and 65.55% at 30%, 25% and 20% dose levels, respectively. At the same dose level (30% dose), the images reconstructed by FBP, PWLS-TV, NLM, BM3D, REDCNN, FBPConvNet and IRLNet algorithms had accuracies for detecting intracerebral hemorrhage of 82.21%, 86.80%, 89.37%, 81.43%, 90.05%, 90.72% and 93.51%, respectively. The images reconstructed by IRLNet at 30%, 25% and 20% dose levels had accuracies for detecting intracerebral hemorrhage of 93.51%, 93.51% and 93.06%, respectively.@*CONCLUSION@#The performance of reconstructed low-dose CT images for detecting intracerebral hemorrhage is significantly affected by both dose and reconstruction algorithms. In clinical practice, choosing appropriate dose level and reconstruction algorithm can greatly reduce the radiation dose and ensure the detection performance of CT imaging for intracerebral hemorrhage.
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Humanos , Algoritmos , Hemorragia Cerebral/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Análisis de los Mínimos Cuadrados , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE@#To evaluate the safety of preoxygenation with high-flow nasal oxygenation in elderly patients during induction of general anesthesia with endotracheal intubation.@*METHODS@#Fifty-six elderly patients without difficult airway were randomized equally into high-flow nasal oxygen group (HF group) and conventional mask oxygen group (M group). Preoxygenation was performed for 5 min before induction of general anesthesia and endotracheal intubation. Oxygenation was maintained during laryngoscopy in HF group, and ventilation lasted until laryngoscopy in M group. For all the patients, the general data, cross-sectional area (CSA) of the gastric antrum measured by ultrasonography, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and arterial oxygen saturation (cSO2) were recorded before preoxygenation (T1), at 5 min of preoxygenation (T2) and immediately after intubation (T3). The safety time of asphyxia, intubation time, times of mask ventilation and postoperative complications were compared between the two groups.@*RESULTS@#The general data were comparable between the two groups. After 5 min of preoxygenation, PaO2 and cSO2 were significantly increased in both groups, and PaO2 was significantly higher in HF group than in M group (F=118.108 vs 9.511, P < 0.05). Both PaO2 and cSO2 decreased after intubation, but PaO2 decreased more slowly in HF group and still remained higher than that at T1; cSO2 decreased significantly in M group to a lower level than that at T1. Compared with those in M group, the patients in HF group showed a significantly longer safety time of asphyxia (t=5.305, P < 0.05) with fewer times of mask ventilation (χ2= 6.720, P < 0.05). PaCO2 increased after intubation in both groups but was comparable between the two groups (F=3.138, P > 0.05).@*CONCLUSION@#High-flow nasal oxygen is safe, simple and effective for pre-oxygenation, which, as compared with the conventional oxygen mask, improves arterial oxygen partial pressure and prolongs the safety time of asphyxia to ensure the safety of airway management during induction of general anesthesia in elderly patients with endotracheal intubation.
Asunto(s)
Anciano , Humanos , Anestesia General , Asfixia , Intubación Intratraqueal , Oxígeno , Presión ParcialRESUMEN
OBJECTIVE@#To explore clinical effect of the first metatarsophalangeal joint fusion combined with lateral toe rotation Weil osteotomy in treating hallux valgus with severe metatarsal adduction.@*METHODS@#From March 2017 to August 2021, 37 patients ( 69 feet ) with severe plantar adductor hallux valgus were treated with the first metatarsophalangeal joint fusion combined with rotational Weil osteotomy were retrospectively analyzed, including 8 males(11 feet) and 29 females (58 feet), aged from 67 to 83 years old with an average of (70.03±2.87) years old;3 cases on the left side, 2 cases on the right side and 32 cases on both sides. Visual analogue scale(VAS) was used to evaluate degree of pain relief before operation, 6 weeks after operation and at the final follow-up. American Orthopaedic Foot and Ankle Surgery (AOFAS) forefoot score was used to evaluate function of the affected foot before operation and final follow-up. Hallux valgus angle(HVA) and intermetatarsal angle(IMA) were measured before operation and at the final follow-up.@*RESULTS@#Thirty-seven patients(69 feet) were followed up from 12 to 48 months with an average of(22.8±0.6) months. Bone healing was achieved at the first metatarsophalangeal joint from 7 to 10 weeks with an average of (8.00±1.21) weeks after operation, without delay and nonunion. HVA was increased from (44.30±2.84)° before operation to (15.20±2.13) °at the final follow-up, and had statistical difference(t=65.781, P<0.05);while no difference in IMA before and after operation(P>0.05). VAS was decreased from (6.73±1.48) points to (2.78±0.71) points at 6 months after operation(t=3.279, P<0.05), and had difference compared with the latest follow-up(1.16±1.12)(t=4.859, P<0.05). AOFAS forefoot score increased from (52.14±5.78) preoperatively to (86.70±4.86) at the fonal follow-up, and 25 feet got excellent results, 40 feet good and 4 feet fair.@*CONCLUSION@#The first metatarsophalangeal joint fusion combined with lateral toe rotation Weil osteotomy in treating severe plantar adduction hallux valgus could significantly relieve pain and appearance of forefoot, stabilize the first sequence, and significantly improve walking function.
Asunto(s)
Masculino , Femenino , Humanos , Anciano , Anciano de 80 o más Años , Huesos Metatarsianos/cirugía , Hallux Valgus/cirugía , Estudios Retrospectivos , Rotación , Resultado del Tratamiento , Osteotomía/métodos , Articulación Metatarsofalángica/cirugía , Juanete , Dedos del PieRESUMEN
Objective To compare the effectiveness of loop-mediated isothermal amplification (LAMP) assay and microscopic examinations for detection of Schistosoma japonicum infections in Oncomelania hupensis in transmission-interrupted regions, so as to provide insights into the optimization of snail surveillance tools in these regions. Methods Four hilly schistosomiasis-endemic villages where transmission interruption was achieved were selected in Heqing County of Yunnan Province as the study villages, including Xinzhuang and Gule villages in hilly regions and Lianyi and Yitou villages in dam regions. Snail survey was performed by means of systematic sampling combined with environmental sampling in July 2018. All captured snails were identified for S. japonicum infections using microscopy. In addition, 10 to 20 snails were randomly sampled from each snail habitat following microscopy, numbered according to environments and subjected to LAMP assay. The positive rate of settings with S. japonicum-infected snails was compared among villages. Results A total of 7 949 living snails were captured from 83 snail habitats in 4 villages, and no S. japonicum infection was detected in snails. There were 226 mixed samples containing 1 786 snails subjected to LAMP assay, and positive LAMP assay was found in 3 mixed samples from 3 snail habitats in 2 dam villages. The positive rates of settings with S. japonicum-infected snails were comparable between Lianyi Village (one setting) and Yitou Village (2 set tings) (5.89% vs. 14.29%, P = 0.344). However, the overall positive rate of settings with S. japonicum-infected snails was significantly higher in dam villages (9.67%, 3/31) than in hilly villages (0) (P = 0.048). Conclusions LAMP assay is more sensitive to detect S. japonicum infections in O. hupensis than conventional microcopy method, which may serve as a supplementary method for detection of S. japonicum infections in O. hupensis in high-risk snail habitats in hilly transmission-interrupted regions.