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1.
Front Oncol ; 14: 1367603, 2024.
Article in English | MEDLINE | ID: mdl-38803532

ABSTRACT

Objectives: The safety and feasibility of repeat biopsy after systemic treatment for non-small cell lung cancer have received extensive attention in recent years. The purpose of this research was to compare complication rates between initial biopsy and rebiopsy in non-small cell lung cancer patients with progressive disease and to assess complication risk factors and clinical results after rebiopsy. Methods: The study included 113 patients initially diagnosed with non-small cell lung cancer who underwent lung biopsy at initial biopsy and rebiopsy after progression while on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and/or chemotherapy from January 2018 to December 2021. We compared the incidence of complications between the initial biopsy and rebiopsy and analyzed the predictors factors that influenced complications in patients who underwent rebiopsy. Results: The successful rate of rebiopsy was 88.5% (100/113). With the exception of two cases where lung adenocarcinoma changed into small cell lung cancer with gefitinib treatment, 98 individuals retained their initial pathological type. The secondary EGFR T790M mutation accounts for 55.6% of acquired resistance. The total number of patients with complications in initial biopsy was 25 (22.1%) and 37 (32.7%) in the rebiopsy. The incidence of pulmonary hemorrhage increased from 7.1% at the initial biopsy to 10.6% at rebiopsy, while the incidence of pneumothorax increased from 14.2% to 20.4%. Compared with the initial biopsy, the incidence of overall complications, parenchymal hemorrhage, and pneumothorax increased by 10.6%, 3.5%, and 6.2%, respectively. In all four evaluations (pneumorrhagia, pneumothorax, pleural reaction, and overall complication), there were no significant differences between the rebiopsy and initial biopsy (all p > 0.05). The multivariate logistic regression analysis suggested that male sex (odds ratio [OR] = 5.064, p = 0.001), tumor size ≤ 2 cm (OR = 3.367, p = 0.013), EGFR-TKIs with chemotherapy (OR = 3.633, p =0.023), and transfissural approach (OR = 7.583, p = 0.026) were independent risk factors for overall complication after rebiopsy. Conclusion: Compared with the initial biopsy, the complication rates displayed a slight, but not significant, elevation in rebiopsy. Male sex, tumor size ≤ 2 cm, transfissural approach, and EGFR-TKIs combined with chemotherapy were independent risk factors for rebiopsy complications.

2.
Methods ; 221: 55-64, 2024 01.
Article in English | MEDLINE | ID: mdl-38061496

ABSTRACT

The detection of complex interactions between single nucleotide polymorphisms (SNPs) plays a vital role in genome-wide association analysis (GWAS). The multi-objective evolutionary algorithm is a promising technique for SNP-SNP interaction detection. However, as the scale of SNP data further increases, the exponentially growing search space gradually becomes the dominant factor, causing evolutionary algorithm (EA)-based approaches to fall into local optima. In addition, multi-objective genetic operations consume significant amounts of time and computational resources. To this end, this study proposes a distributed multi-objective evolutionary framework (DM-EF) to identify SNP-SNP interactions on large-scale datasets. DM-EF first partitions the entire search space into several subspaces based on a space-partitioning strategy, which is nondestructive because it guarantees that each feasible solution is assigned to a specific subspace. Thereafter, each subspace is optimized using a multi-objective EA optimizer, and all subspaces are optimized in parallel. A decomposition-based multi-objective firework optimizer (DCFWA) with several problem-guided operators was designed. Finally, the final output is selected from the Pareto-optimal solutions in the historical search of each subspace. DM-EF avoids the preference for a single objective function, handles the heavy computational burden, and enhances the diversity of the population to avoid local optima. Notably, DM-EF is load-balanced and scalable because it can flexibly partition the space according to the number of available computational nodes and problem size. Experiments on both artificial and real-world datasets demonstrate that the proposed method significantly improves the search speed and accuracy.


Subject(s)
Genome-Wide Association Study , Polymorphism, Single Nucleotide , Polymorphism, Single Nucleotide/genetics , Genome-Wide Association Study/methods , Algorithms
3.
PNAS Nexus ; 2(11): pgad342, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37941810

ABSTRACT

Eukaryotic cells activate the S-phase checkpoint signal transduction pathway in response to DNA replication stress. Affected by the noise in biochemical reactions, such activation process demonstrates cell-to-cell variability. Here, through the analysis of microfluidics-integrated time-lapse imaging, we found multiple S-phase checkpoint activations in a certain budding yeast cell cycle. Yeast cells not only varied in their activation moments but also differed in the number of activations within the cell cycle, resulting in a stochastic multiple activation process. By investigating dynamics at the single-cell level, we showed that stochastic waiting times between consecutive activations are exponentially distributed and independent from each other. Finite DNA replication time provides a robust upper time limit to the duration of multiple activations. The mathematical model, together with further experimental evidence from the mutant strain, revealed that the number of activations under different levels of replication stress agreed well with Poisson distribution. Therefore, the activation events of S-phase checkpoint meet the criterion of Poisson process during DNA replication. In sum, the observed Poisson activation process may provide new insights into the complex stochastic dynamics of signal transduction pathways.

4.
Front Oncol ; 13: 1175010, 2023.
Article in English | MEDLINE | ID: mdl-37706180

ABSTRACT

Purpose: This study aimed to explore the efficacy of the computed tomography (CT) radiomics model for predicting the Ki-67 proliferation index (PI) of pure-solid non-small cell lung cancer (NSCLC). Materials and methods: This retrospective study included pure-solid NSCLC patients from five centers. The radiomics features were extracted from thin-slice, non-enhanced CT images of the chest. The minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to reduce and select radiomics features. Logistic regression analysis was employed to build predictive models to determine Ki-67-high and Ki-67-low expression levels. Three prediction models were established: the clinical model, the radiomics model, and the nomogram model combining the radiomics signature and clinical features. The prediction efficiency of different models was evaluated using the area under the curve (AUC). Results: A total of 211 NSCLC patients with pure-solid nodules or masses were included in the study (N=117 for the training cohort, N=49 for the internal validation cohort, and N=45 for the external validation cohort). The AUC values for the clinical models in the training, internal validation, and external validation cohorts were 0.73 (95% CI: 0.64-0.82), 0.75 (95% CI:0.62-0.89), and 0.72 (95% CI: 0.57-0.86), respectively. The radiomics models showed good predictive ability in diagnosing Ki-67 expression levels in the training cohort (AUC, 0.81 [95% CI: 0.73-0.89]), internal validation cohort (AUC, 0.81 [95% CI: 0.69-0.93]) and external validation cohort (AUC, 0.78 [95% CI: 0.64-0.91]). Compared to the clinical and radiomics models, the nomogram combining both radiomics signatures and clinical features had relatively better diagnostic performance in all three cohorts, with the AUC of 0.83 (95% CI: 0.76-0.90), 0.83 (95% CI: 0.71-0.94), and 0.81 (95% CI: 0.68-0.93), respectively. Conclusion: The nomogram combining the radiomics signature and clinical features may be a potential non-invasive method for predicting Ki-67 expression levels in patients with pure-solid NSCLC.

5.
PLoS Comput Biol ; 19(9): e1011383, 2023 09.
Article in English | MEDLINE | ID: mdl-37656752

ABSTRACT

Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, reflecting increasing severity of COVID-19 disease. We found the numerical product of immune system's ability to clear the virus and to kill the infected cells, namely immune efficacy, to be predictive of disease severity. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results suggested that immune efficacy based on memory T cells and neutralizing antibody titers could be used to predict population vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.


Subject(s)
COVID-19 , Virus Diseases , Humans , COVID-19/prevention & control , SARS-CoV-2 , Viral Load
6.
Ocul Immunol Inflamm ; 31(5): 955-960, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35852938

ABSTRACT

PURPOSE: The purpose of this study was to describe a case series of hypopyon after periorbital corticosteroid injection. METHODS: This was a retrospective, observational case series investigating hypopyon cases after injection of periorbital steroid patients. RESULTS: We presented three patients manifested hypopyon after periocular corticosteroid injection. All three cases were diagnosed as HSV stromal keratitis or endotheliitis and treated successfully with topical steroids as well as systemic and topical antiviral treatment. CONCLUSION: HSV keratitis is not recommend when treated with periocular corticosteroid injection. Topical corticosteroid is the best choice for HSV stromal keratitis and HSV endotheliitis.


Subject(s)
Iridocyclitis , Keratitis, Herpetic , Humans , Antiviral Agents/adverse effects , Keratitis, Herpetic/diagnosis , Keratitis, Herpetic/drug therapy , Glucocorticoids/adverse effects , Iridocyclitis/drug therapy , Administration, Topical
7.
Ocul Immunol Inflamm ; 31(3): 631-634, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35394848

ABSTRACT

PURPOSE: To report a rare case of fungal keratitis caused by Plectosphaerella cucumerina. METHODS: This study retrospectively reviewed the medical records of a case of fungal keratitis. RESULTS: Silt-lamp biomicroscopy revealed corneal infiltration and epithelial defects. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) were performed to assist in the diagnosis and evaluate corneal conditions. The isolate was identified as Plectosphaerella cucumerina by MALDI-TOF mass spectrometry. The patient was treated with topical 5% pimaricin and oral voriconazole for 1 month and recovered. CONCLUSION: Fungal keratitis caused by Plectosphaerella cucumerina is rare. AS-OCT and IVCM can help locate the lesion and diagnose fungal keratitis. Furthermore, MALDI-TOF mass spectrometry showed potential prospects in the identification of filamentous fungi. Plectosphaerella cucumerina rarely infects humans and is sensitive to antifungal agents such as pimaricin and voriconazole.


Subject(s)
Ascomycota , Corneal Diseases , Corneal Ulcer , Eye Infections, Fungal , Keratitis , Humans , Voriconazole/therapeutic use , Natamycin , Keratitis/diagnosis , Keratitis/drug therapy , Keratitis/microbiology , Retrospective Studies , Corneal Ulcer/drug therapy , Antifungal Agents/therapeutic use , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Corneal Diseases/drug therapy
8.
Comput Biol Med ; 151(Pt B): 106303, 2022 12.
Article in English | MEDLINE | ID: mdl-36435056

ABSTRACT

Corneal nerves are of great interest to clinicians and scientists due to their potential for the diagnosis of early neurological disorders. In vivo confocal microscopy (IVCM) has been used as a novel and reliable tool for observing and quantifying corneal sub-basal nerves. Creating a wide-field montage of the nerve plexus from a large amount of IVCM images facilitates the measurement of corneal nerve morphology. In this paper, we propose a fully automatic image stitching method using neural networks. Firstly, we extend a self-supervised point detector to find the feature points on IVCM images. Then a flexible points correspondence based on the attention mechanism is developed for partial assignment of image pair. The scattered IVCM images are consequently integrated and fused according to the local offsets. We experimented with our method on 30 sets of IVCM images. Compared to conventional methods, our method improves matching accuracy and significantly reduces processing time. And by calculating the morphological parameters of the corneal nerve for both single images and stitched images, our method can evaluate the corneal nerve of patients more accurately and reliably. The implemented code is available at https://github.com/LiTianYu6/NerveStitcher.


Subject(s)
Cornea , Neural Networks, Computer , Humans , Cornea/diagnostic imaging , Microscopy, Confocal/methods
9.
iScience ; 25(9): 104911, 2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36060072

ABSTRACT

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by an overactive immune response to self-antigen. The overactivation of CD4+ Foxp3- conventional T cells (Tcons) and the inactivation of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) play important roles in the progression of SLE. Clinical trials showed that low-dose interleukin-2 (IL-2) is effective in treating SLE. Here, we developed a mathematical model involving Tcons, Tregs, natural killer (NK) cells, and IL-2 to simulate the dynamic processes involved in the treatment of SLE. We found an effective range of IL-2 dosage defined by the Tcon/Treg ratio in SLE treatment, termed the IL-2 dosage therapeutic window (IDTW). Our results showed that high levels of self-antigen result in a narrow IDTW and high post-treatment Tcon/Treg ratio. Furthermore, we proposed a classification method based on the ratio of pre-treatment Treg to CD4+ T cells to predict the treatment outcome of SLE patients.

10.
Biomacromolecules ; 23(10): 4153-4166, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-35786865

ABSTRACT

Polyhydroxyalkanoates (PHAs) are microbial polyesters that have the potential to replace nonbiodegradable petroplastics. A real-time in situ PHA quantification method has long been awaited to replace the traditional method, which is time- and labor-consuming. Quantification of PHA in living cells was finally developed from fluorescence intensities generated from the green fluorescence protein (GFP) fused with the Halomonas bluephagenesis phasin proteins. Phasins PhaP1 and PhaP2 were used to fuse with GFP, which reflected PHA accumulation with an R-square of over 0.9. Also, a standard correlation was established to calculate PHA contents based on the fluorescence and cell density recorded via a microplate reader with an R-square of over 0.95 when grown on various substrates. The PhaP2-GFP containing H. bluephagenesis was applied successfully to quantify PHA synthesis in a 7.5 L fermenter with high precision. Moreover, the method was found to be feasible in non-natural PHA producers such as Escherichia coli, demonstrating its broad applicability.


Subject(s)
Polyhydroxyalkanoates , Bacterial Proteins/chemistry , Escherichia coli/genetics , Escherichia coli/metabolism , Fluorescence , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Plant Lectins , Polyesters/metabolism , Polyhydroxyalkanoates/metabolism
11.
Heliyon ; 8(5): e09488, 2022 May.
Article in English | MEDLINE | ID: mdl-35600458

ABSTRACT

The determinants underlying the heterogeneity of coronavirus disease 2019 (COVID-19) remain to be elucidated. To systemically analyze the immunopathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we built a multicompartment mathematical model based on immunological principles and typical COVID-19-related characteristics. This model integrated the trafficking of immune cells and cytokines among the secondary lymphoid organs, peripheral blood and lungs. Our results suggested that early-stage lymphopenia was related to lymphocyte chemotaxis, while prolonged lymphopenia in critically ill patients was associated with myeloid-derived suppressor cells. Furthermore, our model predicted that insufficient SARS-CoV-2-specific naïve T/B cell pools and ineffective activation of antigen-presenting cells (APCs) would cause delayed immunity activation, resulting in elevated viral load, low immunoglobulin level, etc. Overall, we provided a comprehensive view of the dynamics of host immunity after SARS-CoV-2 infection that enabled us to understand COVID-19 heterogeneity from systemic perspective.

12.
Arch Microbiol ; 204(3): 174, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-35166945

ABSTRACT

A bacterial isolate (BGMRC 2046T) was isolated from the rhizosphere soil of Zoysia matrella collected from the Beibu Gulf of China. The results of a polyphasic taxonomic study revealed that this strain belongs to a member of the genus Stappia with the characteristics of Gram-stain-negative, catalase- and oxidase-positive, motile, short rod-shaped. The strain grew at 20-37 °C (optimal, 28 °C), pH 6.0-9.0 (optimal, pH 7.0), and 1-7% (w/v) optimal, NaCl (1-3%). A phylogenetic evaluation based on 16S rRNA gene sequence analysis revealed that this strain fall into the family Stappiaceae, being most closely related to Stappia indica CGMCC 1A01226T (95.8% sequence similarity), Stappia stellulata DSM 5886T (95.1%), and Stappia taiwanensis DSM 23284T (94.4%). The major cellular fatty acid, respiratory quinone and polar lipids were all detected from new species (BGMRC 2046T), that shows the chemical characteristics of BGMRC 2046T. The major polar lipids were two unidentified ninhydrin positive phospholipids, four unidentified phospholipids, and one unidentified lipid. Genome sequencing revealed a genome size of 4.78 Mbp and a G + C content of 60.8%. Pairwise comparison of the genomes of the new strain BGMRC 2046T and the three most closely related strains resulted in gANI values was lower than 75% and a digital DNA-DNA hybridization values was lower than 24%. The strain possessed genes encoding choline uptake and conversion to betaine gene clusters. The results of the polyphasic taxonomic study showed that strain BGMRC 2046T represents a new species of the genus Stappia. The name Stappia sediminis sp. nov. is proposed for the species with the type strain BGMRC 2046T (= KCTC52115T = CGMCC1.17425T).


Subject(s)
Rhizosphere , Soil , Bacterial Typing Techniques , DNA, Bacterial/genetics , Fatty Acids/analysis , Phospholipids/analysis , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
13.
Article in English | MEDLINE | ID: mdl-34865614

ABSTRACT

In recent years, several case-control studies have explored the association between the rs7763881 locus polymorphism of the HULC gene and cancer risk, however, the findings have been inconsistent. Therefore, a meta-analysis was conducted to clarify the association. Relevant case-control studies were obtained from CNKI, Embase, Web of Science and PubMed databases. RevMan software was used to perform data analysis. A total of 8 case-control studies containing 4036 cases and 5286 controls were included in the current meta-analysis. The overall analysis results showed no significant association between the rs7763881 locus polymorphism and cancer risk. However, stratified analysis based on cancer type showed that the rs7763881 locus polymorphism was associated with the decreased risk of hepatocellular cancer, colorectal cancer and esophageal cancer. In conclusion, the current findings suggest that the rs7763881 polymorphic loci located on the HULC gene may serve as a biomarker for determining an individual's risk of hepatocellular cancer, colorectal cancer and esophageal cancer.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms
14.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Article in English | MEDLINE | ID: mdl-34675074

ABSTRACT

Most genetic changes have negligible reversion rates. As most mutations that confer resistance to an adverse condition (e.g., drug treatment) also confer a growth defect in its absence, it is challenging for cells to genetically adapt to transient environmental changes. Here, we identify a set of rapidly reversible drug-resistance mutations in Schizosaccharomyces pombe that are caused by microhomology-mediated tandem duplication (MTD) and reversion back to the wild-type sequence. Using 10,000× coverage whole-genome sequencing, we identify nearly 6,000 subclonal MTDs in a single clonal population and determine, using machine learning, how MTD frequency is encoded in the genome. We find that sequences with the highest-predicted MTD rates tend to generate insertions that maintain the correct reading frame, suggesting that MTD formation has shaped the evolution of coding sequences. Our study reveals a common mechanism of reversible genetic variation that is beneficial for adaptation to environmental fluctuations and facilitates evolutionary divergence.


Subject(s)
Drug Resistance, Fungal/genetics , Schizosaccharomyces/drug effects , Schizosaccharomyces/genetics , Adaptation, Physiological/genetics , DNA, Fungal/genetics , Evolution, Molecular , Genetic Variation , Genome, Fungal , Machine Learning , Mutagenesis, Insertional , Mutation , Reading Frames , Schizosaccharomyces/physiology , Segmental Duplications, Genomic , Tandem Repeat Sequences , Whole Genome Sequencing
15.
BMC Ophthalmol ; 21(1): 211, 2021 May 12.
Article in English | MEDLINE | ID: mdl-33980205

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the in vivo confocal microscopic morphology of corneal subbasal nerves and its relationship with clinical parameters in patients with primary Sjögren's syndrome in China. METHODS: This was a case control study of 22 dry eye disease (DED) patients with primary Sjögren's syndrome (pSS) and 20 control subjects with non-Sjögren dry eye disease (NSDE). Each patient underwent an evaluation of ocular surface disease using the tear film break-up time (TBUT), noninvasive tear film break-up time (NIKBUT), noninvasive tear meniscus height (NIKTMH), corneal staining (National Eye Institute scale, NEI), Schirmer I test, meibography, and corneal subbasal nerve analysis with in vivo confocal microscopy (IVCM). The right eye of each subject was included in this study. RESULTS: SS patients showed a shorter TBUT (P = 0.009) and Schirmer I test results (P = 0.028) than the NSDE group. However, there was no significant difference in NIKBUT between the two groups (P = 0.393). The nerve density of subbasal nerves, number of nerves and tortuosity of the SS group were significantly lower than those of the NSDE group (P = 0.001, P < 0.001 and P = 0.039, respectively). In the SS group, the mean nerve length was correlated with age and the Schirmer I test (r = - 0.519, P = 0.013 and r = 0.463, P = 0.035, respectively). Corneal staining was correlated with nerve density and the number of nerves (r = - 0.534, P = 0.013 and r = - 0.487, P = 0.025, respectively). CONCLUSIONS: Sjögren syndrome dry eye (SSDE) patients have more severe clinical dry eye parameters than non-Sjögren dry eye disease (NSDE) patients. Compared with NSDE patients, we found that SSDE patients showed decreased corneal subbasal nerve density and numbers.


Subject(s)
Dry Eye Syndromes , Sjogren's Syndrome , Case-Control Studies , China/epidemiology , Cornea , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/etiology , Humans , Microscopy, Confocal , Sjogren's Syndrome/complications , Tears
16.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(2): 227-229, 2021 Apr 01.
Article in Chinese | MEDLINE | ID: mdl-33834680

ABSTRACT

Secretory carcinoma, a low-grade malignant tumor, occurs mainly in parotid, submandibular gland, and small salivary glands in the mouth. It has not yet been reported in the mandible. Now we report a case occurred in the right mandibular angle of secretory carcinoma, accompanying with its diagnosis, treatment and prognosis.


Subject(s)
Carcinoma , Salivary Gland Neoplasms , Humans , Mandible , Parotid Gland , Salivary Glands
17.
Phys Rev E ; 101(4-1): 042405, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32422801

ABSTRACT

Biological processes that execute complex multiple functions, such as the cell cycle, must ensure the order of sequential events and maintain dynamic robustness against various fluctuations. Here, we examine the mechanisms and fundamental structure that achieve these properties in the cell cycle of the budding yeast Saccharomyces cerevisiae. We show that this process behaves like an excitable system containing three well-decoupled saddle-node bifurcations to execute DNA replication and mitosis events. The yeast cell-cycle regulatory network can be divided into three modules-the G1/S phase, early M phase, and late M phase-wherein both positive feedback loops in each module and interactions among modules play important roles. Specifically, when the cell-cycle process operates near the critical points of the saddle-node bifurcations, a critical slowing down effect takes place. Such interregnum then allows for an attractive manifold and sufficient duration for cell-cycle events, within which to assess the completion of DNA replication and mitosis, e.g., spindle assembly. Moreover, such arrangement ensures that any fluctuation in an early module or event will not transmit to a later module or event. Thus, our results suggest a possible dynamical mechanism of the cell-cycle process to ensure event order and dynamic robustness and give insight into the evolution of eukaryotic cell-cycle processes.


Subject(s)
Cell Cycle , Models, Biological , Saccharomyces cerevisiae/cytology , DNA Replication , Feedback, Physiological , Kinetics , Saccharomyces cerevisiae/genetics
18.
Transl Vis Sci Technol ; 8(5): 20, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31602345

ABSTRACT

PURPOSE: Subretinal prostheses are a novel technology for restoring useful vision in patients with retinitis pigmentosa or age-related macular degeneration. We characterize the surgical implantation technique and functional time window of an acute rabbit eye model for testing of human subretinal prostheses. METHODS: Retinal prostheses were implanted subretinally in 26 rabbits using a two-step technique. Fundus imaging, fluorescein fundus angiography, and optical coherence topography (OCT) were conducted postoperatively from days 1 to 21 to monitor prosthesis positioning and retinal anatomic changes. RESULTS: Successful implantation and excellent retina apposition were achieved in 84.6% of the rabbits. OCTs showed the overlying retina at full thickness for the first 2 days after implantation. Histology confirmed intact inner layers of the overlying retina until day 3. Progressive atrophy of the overlying retina was revealed by repeated OCTs; approximately 40% of the retina thickness remained on postoperative days 5 and 6. CONCLUSIONS: The two-step implantation technique works well for the rabbit eye model with human prostheses. Rabbit retina may be used for acute electrophysiologic testing of a retinal prosthesis, but is unsuitable for chronic studies due to the merangiotic retina and its limited time window of validity. TRANSLATIONAL RELEVANCE: The improved efficacy in prosthesis surgery using this technique will circumvent the challenges in animal models that provide human-like features critical for the transition into human clinical trials.

19.
J Immunol Res ; 2019: 3642937, 2019.
Article in English | MEDLINE | ID: mdl-31205955

ABSTRACT

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Due to the absence of specific clinical manifestations and biomarkers in the early stage, pSS is generally underrecognized. To elucidate the role of the tissue-specific autoantibodies (TSAs), i.e., anti-CA6, anti-SP1, and anti-PSP antibodies, we enrolled 137 pSS patients, 32 secondary Sjögren's syndrome (sSS) patients, and 127 healthy controls (HCs), whose serum and saliva samples were collected. TSA levels were detected by ELISA, and the clinical and laboratory data was reviewed from the medical records. The analysis results showed the following: (1) Compared to HCs, the serum IgA levels of anti-CA6, anti-SP1 and anti-PSP were significantly higher in pSS as well as in sSS patients, and anti-CA6 IgG was also notably higher in pSS patients. (2) The positivity of anti-CA6, anti-PSP and all the three antibodies together were significantly increased in anti-SSA-negative pSS patients. (3) The average IgM levels of anti-CA6 and anti-SP1 decreased as the disease duration extended. (4) The anti-CA6-positive patients have significantly higher levels of serum IgA, while the anti-PSP-positive group has a notably higher serum IgM level. (5) Another autoantibody specific to the salivary glands, anti-α-fodrin antibody, was elevated in TSA-positive patients, especially in the anti-CA6-positive group. (6) Preliminary detection of saliva TSAs showed that all the IgG levels of these three antibodies increased significantly in pSS patients. In conclusion, TSAs improve diagnosis of pSS in the early stage, especially in anti-SSA-negative patients, and their tissue-specific nature indicates localized salivary injury, which deserves further studies to clarify the mechanism.


Subject(s)
Autoantibodies/blood , Biomarkers/blood , Salivary Glands/pathology , Sjogren's Syndrome/diagnosis , Adult , Aged , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Organ Specificity , Retrospective Studies
20.
Sensors (Basel) ; 18(11)2018 Nov 18.
Article in English | MEDLINE | ID: mdl-30453696

ABSTRACT

The Gaofen-3 (GF-3) satellite is the first C-band multi-polarization synthetic aperture radar (SAR) with the ability of high-accuracy mapping in China. However, the Ground Control Points (GCPs) are essential to ensure the accuracy of mapping for GF-3 SAR imagery at present. In this paper, we analyze the error sources that affect the geometric processing and propose a new block adjustment method without GCPs for GF-3 SAR imagery. Firstly, the geometric calibration of GF-3 image is carried out. Secondly, the rational polynomial coefficient (RPC) model is directly generated after the geometric calibration parameters compensation of each image. Finally, we solve the orientation parameters of the GF-3 images through DEM assisted planar block adjustment and conduct ortho-rectification. With two different imaging modes of GF-3 satellite, which include the QPSI and FS2, we carry out the block adjustment without GCPs. Experimental results of testing areas including Wuhan city and Hubei province in China show that the geometric mosaic accuracy and the absolute positioning accuracy of the orthophoto are better than one pixel, which has laid a good foundation for the application of GF-3 image in global high-accuracy mapping.

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