22 research outputs found

    MTANS:Multi-Scale Mean Teacher Combined Adversarial Network with Shape-Aware Embedding for Semi-Supervised Brain Lesion Segmentation

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    The annotation of brain lesion images is a key step in clinical diagnosis and treatment of a wide spectrum of brain diseases. In recent years, segmentation methods based on deep learning have gained unprecedented popularity, leveraging a large amount of data with high-quality voxel-level annotations. However, due to the limited time clinicians can provide for the cumbersome task of manual image segmentation, semi-supervised medical image segmentation methods present an alternative solution as they require only a few labeled samples for training. In this paper, we propose a novel semi-supervised segmentation framework that combines improved mean teacher and adversarial network. Specifically, our framework consists of (i) a student model and a teacher model for segmenting the target and generating the signed distance maps of object surfaces, and (ii) a discriminator network for extracting hierarchical features and distinguishing the signed distance maps of labeled and unlabeled data. Besides, based on two different adversarial learning processes, a multi-scale feature consistency loss derived from the student and teacher models is proposed, and a shape-aware embedding scheme is integrated into our framework. We evaluated the proposed method on the public brain lesion datasets from ISBI 2015, ISLES 2015, and BRATS 2018 for the multiple sclerosis lesion, ischemic stroke lesion, and brain tumor segmentation respectively. Experiments demonstrate that our method can effectively leverage unlabeled data while outperforming the supervised baseline and other state-of-the-art semi-supervised methods trained with the same labeled data. The proposed framework is suitable for joint training of limited labeled data and additional unlabeled data, which is expected to reduce the effort of obtaining annotated images

    Strong Synergism of Palmatine and Fluconazole/Itraconazole Against Planktonic and Biofilm Cells of Candida Species and Efflux-Associated Antifungal Mechanism

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    Fungal infections caused by Candida albicans and non-albicans Candida [NAC] species are becoming a growing threat in immunodeficient population, people with long-term antibiotic treatment and patients enduring kinds of catheter intervention. The resistance to one or more than one conventional antifungal agents contributes greatly to the widespread propagation of Candida infections. The severity of fungal infection requires the discovery of novel antimycotics and the extensive application of combination strategy. In this study, a group of Candida standard and clinical strains including C. albicans as well as several NAC species were employed to evaluate the antifungal potentials of palmatine (PAL) alone and in combination with fluconazole (FLC)/itraconazole (ITR) by microdilution method, checkerboard assay, gram staining, spot assay, and rhodamine 6G efflux test. Subsequently, the expressions of transporter-related genes, namely CDR1, CDR2, MDR1, and FLU1 for C. albicans, CDR1 and MDR1 for Candida tropicalis and Candida parapsilosis, ABC1 and ABC2 for Candida krusei, CDR1, CDR2, and SNQ2 for Candida glabrata were analyzed by qRT-PCR. The susceptibility test showed that PAL presented strong synergism with FLC and ITR with fractional inhibitory concentration index (FICI) in a range of 0.0049–0.75 for PAL+FLC and 0.0059–0.3125 for PAL+ITR in planktonic cells, 0.125–0.375 for PAL+FLC and 0.0938–0.3125 for PAL+ITR in biofilms. The susceptibility results were also confirmed by gram staining and spot assay. After combinations, a vast quantity of rhodamine 6G could not be pumped out as considerably intracellular red fluorescence was accumulated. Meanwhile, the expressions of efflux-associated genes were evaluated and presented varying degrees of inhibition. These results indicated that PAL was a decent antifungal synergist to promote the antifungal efficacy of azoles (such as FLC and ITR), and the underlying antifungal mechanism might be linked with the inhibition of efflux pumps and the elevation of intracellular drug content

    Extraction of Extracellular Matrix in Static and Dynamic Candida Biofilms Using Cation Exchange Resin and Untargeted Analysis of Matrix Metabolites by Ultra-High-Performance Liquid Chromatography-Tandem Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS)

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    Fungal infections caused by Candida albicans poses a great threat to human health. The ability of biofilm formation is believed to be associated with resistance-related Candida infections. Currently, knowledge on extracellular matrix (EM) of C. albicans biofilm is limited. In this study, we introduced ion exchange resin, i.e., cation exchange resin (CER) and anion exchange resin (AER), in EM extraction of C. albicans biofilm as well as several non-albicans Candida (NAC) biofilms under static and dynamic states in combination with vortexing and ultrasonication (VU). The metabolites extracted from the dynamic C. albicans biofilm matrix using the CER-VU and VU were identified with ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) via untargeted filtration. Compared with other physical and chemical extraction methods, CER-VU was demonstrated to be an ideal approach with high-yield acquisitions of EM constituents including proteins, triglycerides and carbohydrates and low-level damages on fungal cell viability and integrity. The untargeted MS analysis further showed the high efficacy of CER-VU, as a large quantity of metabolites (217 versus 198) was matched comprising a great number of lipids, carbohydrates, amino acids, nucleic acids and their derivatives together with a high involvement of signaling pathways compared with the VU alone. However, combining the results from both the CER-VU and VU methods could generate more metabolites. In summary, the EM analysis of the dynamic C. albicans biofilm expands our understanding upon a comprehensive depiction of matrix components and provides another effective approach for EM extraction

    Effects of stellate ganglion block on perimenopausal hot flashes: a randomized controlled trial

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    BackgroundHot flashes are common symptoms afflicting perimenopausal women. A stellate ganglion block (SGB) is believed to be an effective treatment for hot flashes; however, more evidence is needed to evaluate its safety and efficacy in relieving perimenopausal hot flashes.ObjectiveTo investigate the efficacy and safety of SGB for the treatment of perimenopausal hot flashes.MethodsA randomized controlled trial was conducted at Shanxi Bethune Hospital. Forty perimenopausal women with hot flashes were recruited from April 2022 to November 2022 and randomly assigned to receive either 6 consecutive SGB treatments or 6 consecutive saline placebo treatments. The primary outcome was the change in hot flash symptom score from baseline to 12 weeks after treatment. The secondary outcomes were the change in hot flash symptom score from baseline to 12 weeks after treatment and the post-treatment Kupperman Index (KI) and Pittsburgh Sleep Quality Index (PSQI) scores.ResultsOf the 40 randomized subjects, 35 completed the study. All the variables were significantly improved. During 12 weeks of follow-up, the hot flash scores, Kupperman Menopause Scale scores, and Pittsburgh Sleep Quality Scale scores decreased significantly. Two subjects in the SGB treatment group experienced transient hoarseness, and the incidence of related adverse events was 10%. No related adverse events occurred in the control group.ConclusionCompared to the control treatment, SGB treatment was a safe and effective nonhormone replacement therapy that significantly relieved perimenopausal hot flashes and effectively improved sleep quality. Additional studies are needed to assess the long-term efficacy of this therapy

    Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population

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    <p>Abstract</p> <p>Background</p> <p>The blood-derived RNA levels of the adenylosuccinate synthase (<it>ADSS</it>) and ataxia telangiectasia mutated (<it>ATM</it>) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and <it>ADSS </it>and <it>ATM </it>were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes.</p> <p>Methods</p> <p>Six SNPs in the <it>ADSS </it>gene and three SNPs in the <it>ATM </it>gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform.</p> <p>Results</p> <p>There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the <it>ADSS </it>gene and rs227061 and rs664143 in the <it>ATM </it>gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10.</p> <p>Conclusion</p> <p>These findings suggest that the combined effects of the polymorphisms in the <it>ADSS </it>and <it>ATM </it>genes may confer susceptibility to the development of SZ in a Chinese population.</p

    Antiproliferation of berberine in combination with fluconazole from the perspectives of reactive oxygen species, ergosterol and drug efflux in a fluconazole-resistant Candida tropicalis isolate

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    Candida tropicalis has emerged as an important pathogenic fungi in nosocomial infections due to its recalcitrant resistance to conventional antifungal agents, especially to fluconazole (FLC). Berberine (BBR) is a bioactive herbal-originated alkaloids and has been reported to possess antifungal functions against Candida albicans. In this paper, we tried to figure out the antifungal mechanisms of BBR and/or FLC in a clinical C. tropicalis isolate 2006. In the microdilution test, the minimum inhibitory concentration (MIC) of BBR was found 16 μg/mL with fractional inhibitory concentration index (FICI) 0.13 in C. tropicalis 2006. The synergism of BBR and FLC was also confirmed microscopically. After the treatments of BBR and/or FLC, the studies revealed that (i) FLC facilitated BBR to increase reactive oxygen species (ROS), (ii) FLC enhanced the intranuclear accumulation of BBR, (iii) BBR decreased the extracellular rhodamine 123 (Rh123) via inhibiting efflux transporters, (iv) FLC assisted BBR to reduce ergosterol content, and (v) BBR in combined with FLC largely downregulated the expressions of Candida drug resistance 1 (CDR1) and CDR2 but impact slightly multidrug resistance 1 (MDR1), and upregulate the expression of ergosterol 11 (ERG11). These results suggested that BBR could become a potent antifungal drug to strengthen FLC efficacy in FLC-resistant C. tropicalis via ROS increase, intracellular BBR accumulation, ergosterol decrease and efflux inhibition

    Characteristics of sodium and water retention in rats with nephrotic syndrome induced by puromycin aminonucleoside

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    Abstract Introduction Nephrotic syndrome (NS) is characterized by renal sodium and water retention. The mechanisms are not fully elucidated. Methods The NS rat model was established by single intraperitoneal injection of 100 mg/kg puromycin aminonucleoside (PAN). The plasma electrolyte level and urinary sodium excretion were monitored dynamically. The changes of some sodium transporters, including epithelial Na+ channel (ENaC), Na+/H+ exchanger 3 (NHE3), Na+-K+-2Cl− cotransporter 2 (NKCC2) and Na+-Cl− cotransporter (NCC) in renal cortex at different time points and the level of peripheral circulation factors were detected. Results The urinary sodium excretion of the model group increased significantly on the first day, then decreased compared with the control group, and there was no significant difference between the model group and the control group on the 12th day. The changes of peripheral circulation factors were not obvious. Some sodium transporters in renal cortex increased in varying degrees, while NKCC2 decreased significantly compared with the control group. Conclusions The occurrence of NS edema may not be related to the angiotensin system. The decrease of urinary sodium excretion is independent of the development of albuminuria. During the 18 days of observation, it can be divided into three stages: sodium retention, sodium compensation, and simple water retention. The mechanism is related to the increased expression of α-ENaC, γ-ENaC, NHE3 and NCC in a certain period of time, the compensatory decrease of NKCC2 expression and the continuous increase of aquaporin 2 (AQP2) expression
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