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1.
Opt Express ; 32(5): 8101-8121, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38439476

It is extremely challenging to rapidly and accurately extract target echo photon signals from massive photon point clouds with strong background noise without any prior geographic information. Herein, we propose a fast surface detection method realized by combining the improved density-dimension algorithm (DDA) and Kalman filtering (KF), termed the DDA-KF algorithm, for photon signals with a high background noise rate (BNR) to improve the extraction of surface photon signals from spacecraft platforms. The results showed that the algorithm exhibited good adaptability to strong background noise and terrain slope variations, and had real-time processing capabilities for massive photon point clouds in large-scale detection range without prior altitude information of target. Our research provides a practical technical solution for single-photon lidar applications in deep space navigation and can help improve the performance in environments characterized by strong background noise.

2.
Nat Struct Mol Biol ; 31(3): 436-446, 2024 Mar.
Article En | MEDLINE | ID: mdl-38182928

Palmitoylation of cysteine residues at the C-terminal hypervariable regions in human HRAS and NRAS, which is necessary for RAS signaling, is catalyzed by the acyltransferase DHHC9 in complex with its accessory protein GCP16. The molecular basis for the acyltransferase activity and the regulation of DHHC9 by GCP16 is not clear. Here we report the cryo-electron microscopy structures of the human DHHC9-GCP16 complex and its yeast counterpart-the Erf2-Erf4 complex, demonstrating that GCP16 and Erf4 are not directly involved in the catalytic process but stabilize the architecture of DHHC9 and Erf2, respectively. We found that a phospholipid binding to an arginine-rich region of DHHC9 and palmitoylation on three residues (C24, C25 and C288) were essential for the catalytic activity of the DHHC9-GCP16 complex. Moreover, we showed that GCP16 also formed complexes with DHHC14 and DHHC18 to catalyze RAS palmitoylation. These findings provide insights into the regulatory mechanism of RAS palmitoyltransferases.


Lipoylation , Saccharomyces cerevisiae , Humans , Lipoylation/physiology , Cryoelectron Microscopy , Saccharomyces cerevisiae/metabolism , Acyltransferases/metabolism , Membrane Proteins/metabolism
3.
Methods Mol Biol ; 2712: 9-17, 2023.
Article En | MEDLINE | ID: mdl-37578692

Ferroptosis is emerging as a promising strategy for suppressing multiple types of human cancers. Rapid and accurate assessment of the relative sensitivity to ferroptosis in biological samples will accelerate the development of ferroptosis-targeted therapies. We previously demonstrated that photochemical activation of membrane lipid peroxidation (PALP) that uses high-power lasers to induce localized polyunsaturated fatty acyl (PUFA)-lipid peroxidation can efficiently report ferroptosis sensitivity in live cells and tissues in situ. Here, we describe the experimental details for PALP analysis, including preparation of tissue sections, preparation of fluorescent lipid peroxidation reporter, sample staining, lipid peroxidation induced by laser source, and data processing. We envision predicting the relative sensitivity to ferroptosis of cellular and tissue samples is potentially useful for basic research and clinical investigations.


Ferroptosis , Neoplasms , Humans , Lipid Peroxidation/physiology
4.
Nat Med ; 29(6): 1530-1539, 2023 Jun.
Article En | MEDLINE | ID: mdl-37264205

Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.


Lymphatic Abnormalities , Vascular Malformations , Humans , Mutation , Genetic Testing/methods , Vascular Malformations/diagnosis , Vascular Malformations/genetics , Vascular Malformations/therapy , Alleles , Lymphatic Abnormalities/genetics , Genomics
5.
Anal Chim Acta ; 1254: 341045, 2023 May 08.
Article En | MEDLINE | ID: mdl-37005014

A microdots array-based fluoremetric method with superwettability profile has been developed for the simultaneous and separate detection of Fe3+ and Cu2+ ions in red wine samples. A wettable micropores array was initially designed with high density by using polyacrylic acid (PAA) and hexadecyltrimethoxysilane (HDS), followed by the NaOH etching route. Zinc metal organic frameworks (Zn-MOFs) were fabricated as the fluorescent probes to be immobilized into the micropores array to obtain the fluoremetric microdots array platform. It was found that the fluorescence of Zn-MOFs probes could decrease significantly in the presence of Fe3+ and/or Cu2+ ions towards their simultaneous analysis. Yet, the specific responses to Fe3+ ions could be expected if using histidine to chelate Cu2+ ions. Moreover, the developed Zn-MOFs-based microdots array with superwettability profile can enable the accumulation of targeting ions from the complicated samples without any tedious pre-processing. Also, the cross-contamination of different samples droplets can be largely avoided so as to facilitate the analysis of multiple samples. Subsequently, the feasibility of simultaneous and separate detection of Fe3+ and Cu2+ ions in red wine samples was demonstrated. Such a design of microdots array-based detection platform may promise the wide applications in analyzing Fe3+ and/or Cu2+ ions in the fields of food safety, environmental monitoring, and medical diseases diagnostics.


Iron , Wine , Iron/analysis , Copper/analysis , Wine/analysis , Zinc/analysis , Ions/analysis
6.
Genes (Basel) ; 14(1)2023 01 04.
Article En | MEDLINE | ID: mdl-36672883

BACKGROUND: Peripheral blood mononuclear cells (PBMCs) are widely used as a model in the study of different human diseases. There is often a time delay from blood collection to PBMC isolation during the sampling process, which can result in an experimental bias, particularly when performing single cell RNA-seq (scRNAseq) studies. METHODS: This study examined the impact of different time periods from blood draw to PBMC isolation on the subsequent transcriptome profiling of different cell types in PBMCs by scRNAseq using the 10X Chromium Single Cell Gene Expression assay. RESULTS: Examining the five major cell types constituting the PBMC cell population, i.e., CD4+ T cells, CD8+ T cells, NK cells, monocytes, and B cells, both common changes and cell-type-specific changes were observed in the single cell transcriptome profiling over time. In particular, the upregulation of genes regulated by NF-kB in response to TNF was observed in all five cell types. Significant changes in key genes involved in AP-1 signaling were also observed. RBC contamination was a major issue in stored blood, whereas RBC adherence had no direct impact on the cell transcriptome. CONCLUSIONS: Significant transcriptome changes were observed across different PBMC cell types as a factor of time from blood draw to PBMC isolation and as a consequence of blood storage. This should be kept in mind when interpreting experimental results.


Leukocytes, Mononuclear , Single-Cell Gene Expression Analysis , Humans , Leukocytes, Mononuclear/metabolism , Gene Expression Profiling , Transcriptome , Killer Cells, Natural
7.
Nanomaterials (Basel) ; 12(23)2022 Nov 25.
Article En | MEDLINE | ID: mdl-36500806

LEDs for plant lighting have attracted wide attention and phosphors with good stability and deep-red emission are urgently needed. Novel Cr3+ and Dy3+ co-doped Gd3Al4GaO12 garnet (GAGG) phosphors were successfully prepared through a conventional solid-state reaction. Using blue LEDs, a broadband deep-red emission at 650−850 nm was obtained due to the Cr3+ 4T2 → 4A2 transition. When the Cr3+ concentration was fixed to 0.1 mol, the crystal structure did not change with an increase in the Dy3+ doping concentration. The luminous intensity of the optimized GAGG:0.1Cr3+, 0.01Dy3+ was 1.4 times that of the single-doped GAGG:0.1Cr3+. Due to the energy transfer from Dy3+ to Cr3+, the internal quantum efficiency reached 86.7%. The energy transfer from Dy3+ to Cr3+ can be demonstrated through luminescence spectra and fluorescence decay. The excellent properties of the synthesized phosphor indicate promising applications in the agricultural industry.

8.
J Mater Chem B ; 10(48): 10075-10082, 2022 12 14.
Article En | MEDLINE | ID: mdl-36458484

Covalent organic frameworks (COFs) were fabricated with a hierarchical flower-like hollow structure, possessing a large specific surface area, high porosity, and excellent environmental stability. In situ growth of noble silver nanoparticles (AgNPs) onto COFs was conducted yielding COF-Ag nanozymes. The structural advantages of COFs can ensure the uniform dispersion and effective size control of AgNPs. More interestingly, the oxidase-like catalytic activity of the obtained COF-Ag nanozymes could be enhanced in the presence of Hg2+ ions, which could specifically interact with AgNPs to form Ag-Hg alloys. A COF-Ag catalysis-based colorimetric platform was thereby constructed for highly selective and sensitive analysis of Hg2+ ions, showing a linear concentration range from 0.050 to 10.0 µM, with a limit of detection of about 3.7 nM. Besides, the developed colorimetric strategy was successfully applied for detecting Hg2+ ions in human blood with favorable detection recoveries, indicating its potential for applications in the biomedical analysis, environmental monitoring, and food safety fields.


Mercury , Metal Nanoparticles , Metal-Organic Frameworks , Humans , Colorimetry , Mercury/analysis , Silver/chemistry , Metal Nanoparticles/chemistry , Oxidoreductases , Ions
9.
Int J Ophthalmol ; 15(8): 1305-1309, 2022.
Article En | MEDLINE | ID: mdl-36017041

AIM: To compare the efficacy of vitrectomy combined with air or silicone oil in the treatment of idiopathic macular hole (IMH). METHODS: According to the results of high-definition optical coherence tomography (HD-OCT), 75 cases (75 eyes) of IMH in stage II-IV (Gass stage) in the General Hospital of Chinese PLA from January 2017 to December 2019 were collected for this retrospective study. The best corrected visual acuity (BCVA) and minimum diameter of IMH (MMHD) were measured. Eyes underwent vitrectomy combined with internal limiting membrane peeling operation, and were divided into disinfection air group (30 eyes) and silicone oil group (45 eyes) according to the intraocular tamponade. For MMHD≤400 µm (MMHD1), there were 23 eyes in air group and 16 eyes in silicone oil group. For MMHD2>400 µm (MMHD2), there were 7 eyes in air group and 29 eyes in silicone oil group. One month after surgery, the closure rates of IMH and BCVA were compared and analyzed. According to HD-OCT, the closure shape was graded with A (bridge closure) and B (good closure). RESULTS: The closure rates of air group and silicone oil group were 86.67% and 95.56% respectively with no significant difference (P>0.05); For MMHD1, those of air group and silicone oil group were 95.65% and 100% respectively with no significant difference (P>0.05); For MMHD2, those of air group and silicone oil group were 57.14% and 93.10% respectively, and those of the silicone oil group were higher than the air group (P<0.05). There was no significant difference in the closure shape grade between MMHD1 air group and silicone oil group (P>0.05). The proportion of Grade B in MMHD2 silicone oil group was higher than that in the air group (P<0.05). BCVA of each group after operation was better than that before operation, and there was no significant difference between air group and silicone oil group. While among them, MMHD1 air group was better than silicone oil group (P<0.05), and there was no significant difference between MMHD2 air group and silicone oil group (P>0.05). CONCLUSION: For smaller IMH (≤400 µm), the efficacy of vitrectomy combined with air should be considered better than silicone oil; for larger IMH (>400 µm), the efficacy of silicone oil may be better than air.

10.
Semin Ophthalmol ; 37(6): 767-773, 2022 Aug.
Article En | MEDLINE | ID: mdl-35862571

PURPOSE: The present study assessed the treatment of and risk factors for suprachoroidal hemorrhage (SCH) and reported the outcomes of drainage surgery with vitrectomy in a consecutive series of patients. METHODS: Retrospective case series were carried out to investigate the clinical data of 12 eyes from 12 patients who underwent suprachoroidal hemorrhage drainage with vitrectomy surgery over a 10-year period (from 2010 to 2020). The records of these patients were analyzed, including ophthalmologic examination, ophthalmologic ultrasonography, surgical procedures, and outcome measurements. RESULTS: Twelve consecutive patients with a mean age of 56.5 years were studied. Intraocular surgery, high myopia, glaucoma, hypertension and anticoagulant therapy were the most common risk factors for SCH. All patients underwent external drainage and pars plana vitrectomy surgery. All of the patients were followed up for 10.2 months. Overall, the mean preoperative BCVA improved from 2.3 LogMAR to 1.7 LogMAR at the last follow-up visit (P = .041). CONCLUSIONS: The risk factors for SCH include high myopia, glaucoma, hypertension and anticoagulant therapy. Drainage of SCH with vitrectomy is a valuable approach in the management of SCH.


Choroid Hemorrhage , Drainage , Vitrectomy , Anticoagulants , Choroid Hemorrhage/surgery , Drainage/methods , Glaucoma/surgery , Humans , Hypertension/complications , Middle Aged , Myopia/surgery , Retrospective Studies , Visual Acuity , Vitrectomy/methods
11.
Front Neurorobot ; 16: 889308, 2022.
Article En | MEDLINE | ID: mdl-35770274

In the field of ship image recognition and classification, traditional algorithms lack attention to the differences between the grain of ship images. The differences in the hull structure of different categories of ships are reflected in the coarse-grain, whereas the differences in the ship equipment and superstructures of different ships of the same category are reflected in the fine-grain. To extract the ship features of different scales, the multi-scale paralleling CNN oriented on ships images (SMS-PCNN) model is proposed in this paper. This model has three characteristics. (1) Extracting image features of different sizes by parallelizing convolutional branches with different receptive fields. (2) The number of channels of the model is adjusted two times to extract features and eliminate redundant information. (3) The residual connection network is used to extend the network depth and mitigate the gradient disappearance. In this paper, we collected open-source images on the Internet to form an experimental dataset and conduct performance tests. The results show that the SMS-PCNN model proposed in this paper achieves 84.79% accuracy on the dataset, which is better than the existing four state-of-the-art approaches. By the ablation experiments, the effectiveness of the optimization tricks used in the model is verified.

12.
STAR Protoc ; 3(2): 101189, 2022 06 17.
Article En | MEDLINE | ID: mdl-35345595

Ferroptosis is a non-apoptotic iron-dependent cell death. Here we present a protocol for stratifying ferroptosis sensitivity in cells and mouse tissues. This protocol uses photochemical activation of lipid peroxidation (PALP) coupled with fluorescent imaging to assess the relative sensitivity to ferroptosis. Using commercial reagents and common equipment, PALP is readily accessible to most laboratories. One remaining challenge is the inability to multiplex this technique in analyzing multiple tissues or regions simultaneously. This protocol may have applications in developing ferroptosis-targeted therapies. For complete details on the use and execution of this protocol, please refer to Wang et al. (2021).


Ferroptosis , Animals , Iron/metabolism , Lipid Peroxidation , Mice
13.
Arthritis Rheumatol ; 74(8): 1420-1429, 2022 08.
Article En | MEDLINE | ID: mdl-35347896

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common chronic immune-mediated joint disease among children and encompasses a heterogeneous group of immune-mediated joint disorders classified into 7 subtypes according to clinical presentation. However, phenotype overlap and biologic evidence suggest a shared mechanistic basis between subtypes. This study was undertaken to systematically investigate shared genetic underpinnings of JIA subtypes. METHODS: We performed a heterogeneity-sensitive genome-wide association study encompassing a total of 1,245 JIA cases (classified into 7 subtypes) and 9,250 controls, followed by fine-mapping of candidate causal variants at each genome-wide significant locus, functional annotation, and pathway and network analysis. We further identified candidate drug targets and drug repurposing opportunities by in silico analyses. RESULTS: In addition to the major histocompatibility complex locus, we identified 15 genome-wide significant loci shared between at least 2 JIA subtypes, including 10 novel loci. Functional annotation indicated that candidate genes at these loci were expressed in diverse immune cell types. CONCLUSION: This study identified novel genetic loci shared by JIA subtypes. Our findings identified candidate mechanisms underlying JIA subtypes and candidate targets with drug repurposing opportunities for JIA treatment.


Arthritis, Juvenile , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/genetics , Genetic Loci , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Polymorphism, Single Nucleotide
14.
J Neurosci Methods ; 365: 109389, 2022 01 01.
Article En | MEDLINE | ID: mdl-34687797

BACKGROUND: There is growing interest in the neuroscience community in estimating and mapping microscopic properties of brain tissue non-invasively using magnetic resonance measurements. Machine learning methods are actively investigated to predict the signals measured in diffusion magnetic resonance imaging (dMRI). NEW METHOD: We applied the neural architecture search (NAS) to train a recurrent neural network to generate a multilayer perceptron to predict the dMRI data of unknown signals based on the different acquisition parameters and training data. The search space of NAS is the number of neurons in each layer of the multilayer perceptron network. To our best knowledge, this is the first time to apply NAS to solve the dMRI signal prediction problem. RESULTS: The experimental results demonstrate that the proposed NAS method can achieve fast training and predict dMRI signals accurately. For dMRI signals with four acquisition strategies of double diffusion encoding (DDE), double oscillating diffusion encoding (DODE), multi-shell and DSI-like pulsed gradient spin-echo (PGSE), the mean squared errors of the multilayer perceptron network designed by NAS are 0.0043, 0.0034, 0.0147 and 0.0199, respectively. COMPARISON WITH EXISTING METHOD(S): We also compared NAS with other machine learning prediction methods, such as support vector regression (SVR), decision tree (DT) and random forest (RF), k-nearest neighbors (KNN), adaboost regressor (AR), gradient boosting regressor (GBR) and extra-trees regressor (ET). NAS achieved the better prediction performance in most cases. CONCLUSION: In this study, NAS was developed for the prediction of dMRI signals and could become an effective prediction tool.


Diffusion Magnetic Resonance Imaging , Neural Networks, Computer , Brain/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methods , Machine Learning
15.
Cell Chem Biol ; 29(1): 157-170.e6, 2022 01 20.
Article En | MEDLINE | ID: mdl-34813762

Ferroptosis is an emerging cancer suppression strategy. However, how to select cancer patients for treating with ferroptosis inducers remains challenging. Here, we develop photochemical activation of membrane lipid peroxidation (PALP), which uses targeted lasers to induce localized polyunsaturated fatty acyl (PUFA)-lipid peroxidation for reporting ferroptosis sensitivity in cells and tissues. PALP captured by BODIPY-C11 can be suppressed by lipophilic antioxidants and iron chelation, and is dependent on PUFA-lipid levels. Moreover, we develop PALPv2, for studying lipid peroxidation on selected membranes along the z axis in live cells using two-photon microscopes. Using PALPv1, we detect PUFA-lipids in multiple tissues, and validate a PUFA-phospholipid reduction during muscle aging as previously reported. Patterns of PALPv1 signals across multiple cancer cell types in vitro and in vivo are concordant with their ferroptosis susceptibility and PUFA-phospholipid levels. We envision that PALP will enable rapid stratification of ferroptosis sensitivity in cancer patients and facilitate PUFA-lipid research.


Ferroptosis , Animals , Cells, Cultured , Fatty Acids, Unsaturated/analysis , Fluorescence , Lipid Peroxidation , Lipids/chemistry , Male , Mice , Mice, Inbred C57BL , Microscopy, Fluorescence, Multiphoton , Neoplasms, Experimental/diagnostic imaging
16.
Micromachines (Basel) ; 14(1)2022 Dec 20.
Article En | MEDLINE | ID: mdl-36677065

Aiming at the dynamic testing of the ignition temperature of micro-initiating explosives, a novel Pt-Rh10/Pt thin-film thermocouple was designed in this paper. The author carried out the preparation of the thermocouple by using a screen printing process on an Al2O3 ceramic substrate. The formed thermocouple was made of Pt-Rh10 wire and Pt wire as compensation wires, with a size of ≤ 1 mm and a thickness of about 6 µm. In the testing process, the static calibration of the thermocouple at 50~600 °C and 650~1500 °C was completed by a portable temperature verification furnace and a horizontal high temperature verification furnace, and the results showed that the Seebeck coefficient of the thermocouple was about 10.70 µV/°C, and its output voltage-temperature curve was similar to that of a standard S-type thermocouple, which achieved the effective temperature measurement up to 1500 °C. The dynamic response of Pt-Rh10/Pt thin-film thermocouple was then tested and studied using the pulsed laser method, and the results show that the time constant of the thermocouple prepared in this paper is about 535 µs, which has the characteristics of fast response and high precision high-temperature testing. Compared with the traditional thin-film thermocouple, the thermocouple has excellent electrical conductivity, more oxidation resistance, the surface layer is not easy to peel off and other advantages.

17.
Article En | MEDLINE | ID: mdl-34539796

Partial hepatectomy under general anesthesia is prone to hemodynamic alterations, and stress reactions are the main contributing factors to postoperative cognitive function in elderly partial hepatectomy patients. Postoperative cognitive dysfunction increases the incidence of postoperative complications and long-term morbidity and mortality in elderly patients. With the increasing trend of aging population and the gradual increase of elderly people undergoing surgical treatment, it is especially important to study the corresponding prevention and treatment measures. In this study, a total of 90 patients with primary liver cancer who received hepatectomy in our hospital from July 2020 to July 2021 were included as the research subject. The changes in hemorheology, stress-related indexes, cognitive function, postoperative pain, and gastrointestinal function were compared between the two groups The results showed that SGB combined with general anesthesia can effectively reduce hemodynamic fluctuations in elderly partial hepatectomy patients, alleviate surgical stress, promote postoperative recovery of cognitive function and gastrointestinal function with high safety, and is worthy of clinical promotion.

18.
Neuroimage ; 240: 118367, 2021 10 15.
Article En | MEDLINE | ID: mdl-34237442

Diffusion MRI (dMRI) has become an invaluable tool to assess the microstructural organization of brain tissue. Depending on the specific acquisition settings, the dMRI signal encodes specific properties of the underlying diffusion process. In the last two decades, several signal representations have been proposed to fit the dMRI signal and decode such properties. Most methods, however, are tested and developed on a limited amount of data, and their applicability to other acquisition schemes remains unknown. With this work, we aimed to shed light on the generalizability of existing dMRI signal representations to different diffusion encoding parameters and brain tissue types. To this end, we organized a community challenge - named MEMENTO, making available the same datasets for fair comparisons across algorithms and techniques. We considered two state-of-the-art diffusion datasets, including single-diffusion-encoding (SDE) spin-echo data from a human brain with over 3820 unique diffusion weightings (the MASSIVE dataset), and double (oscillating) diffusion encoding data (DDE/DODE) of a mouse brain including over 2520 unique data points. A subset of the data sampled in 5 different voxels was openly distributed, and the challenge participants were asked to predict the remaining part of the data. After one year, eight participant teams submitted a total of 80 signal fits. For each submission, we evaluated the mean squared error, the variance of the prediction error and the Bayesian information criteria. The received submissions predicted either multi-shell SDE data (37%) or DODE data (22%), followed by cartesian SDE data (19%) and DDE (18%). Most submissions predicted the signals measured with SDE remarkably well, with the exception of low and very strong diffusion weightings. The prediction of DDE and DODE data seemed more challenging, likely because none of the submissions explicitly accounted for diffusion time and frequency. Next to the choice of the model, decisions on fit procedure and hyperparameters play a major role in the prediction performance, highlighting the importance of optimizing and reporting such choices. This work is a community effort to highlight strength and limitations of the field at representing dMRI acquired with trending encoding schemes, gaining insights into how different models generalize to different tissue types and fiber configurations over a large range of diffusion encodings.


Brain/diagnostic imaging , Databases, Factual , Diffusion Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods , Neural Networks, Computer , Animals , Brain/physiology , Humans , Mice
19.
Comput Math Methods Med ; 2021: 9987067, 2021.
Article En | MEDLINE | ID: mdl-34257703

Lung cancer has a high mortality rate. Promoting early diagnosis and screening of lung cancer is the most effective way to enhance the survival rate of lung cancer patients. Through computer technology, a comprehensive evaluation of genetic testing results and basic clinical information of lung cancer patients could effectively diagnose early lung cancer and indicate cancer risks. This study retrospectively collected 70 pairs of lung cancer tissue samples and normal human tissue samples. The methylation frequencies of 6 genes (FHIT, p16, MGMT, RASSF1A, APC, DAPK) in lung cancer patients, the basic clinical information, and tumor marker levels of these patients were analyzed. Then, the python package "sklearn" was employed to build a support vector machine (SVM) classifier which performed 10-fold cross-validation to construct diagnostic models that could identify lung cancer risk of suspected cases. Receiver operation characteristic (ROC) curves were drawn, and the performance of the combined diagnostic model based on several factors (clinical information, tumor marker level, and methylation frequency of 6 genes in blood) was shown to be better than that of models with only one pathological feature. The AUC value of the combined model was 0.963, and the sensitivity, specificity, and accuracy were 0.900, 0.971, and 0.936, respectively. The above results revealed that the diagnostic model based on these features was highly reliable, which could screen and diagnose suspected early lung cancer patients, contributing to increasing diagnosis rate and survival rate of lung cancer patients.


Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , DNA Methylation/genetics , Diagnosis, Computer-Assisted/methods , Early Detection of Cancer/methods , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Support Vector Machine , Adult , Aged , Aged, 80 and over , Case-Control Studies , Computational Biology , Diagnosis, Computer-Assisted/statistics & numerical data , Early Detection of Cancer/statistics & numerical data , Female , Humans , Lung Neoplasms/blood , Male , Middle Aged , ROC Curve , Retrospective Studies
20.
J Ethnopharmacol ; 270: 113646, 2021 Apr 24.
Article En | MEDLINE | ID: mdl-33264659

ETHNOPHARMACOLOGICAL RELEVANCE: As a classic herbal prescription, Huanglian Jiedu Decoction (HLJDD) exhibits positive effects against cardiac dysfunction. However, its cardioprotective effects and potential mechanism(s) of action still need to be systematically investigated. AIM OF THE STUDY: This study aimed to reveal the underlying therapeutic mechanism of HLJDD on transverse aortic constriction (TAC)-induced pathological cardiac hypertrophy and remodeling. MATERIALS AND METHODS: TAC-induced cardiac hypertrophy and remodeling mice model was established to evaluate the therapeutic effects of HLJDD. Serum untargeted metabolomics and lipidomic profiling were performed using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry coupled with multivariate statistical analyses. RESULTS: Oral administration of HLJDD (2.5 g/kg/day, 5.0 g/kg/day) significantly improved the heart morphology, enhanced the heart function, and alleviated the accumulation of fibrosis in the interstitial space and the infiltration of inflammatory cells in TAC-stimulated mice. Serum untargeted metabolomics analysis showed that significant alterations were observed in metabolic signatures between the TAC-model and sham group. Principal component analysis and orthogonal partial least-squares discriminant analysis screened 59 differential metabolic features and 13 metabolites were identified. The disturbed metabolic pathways in TAC group mainly related to lipid metabolism. Further serum lipidomic profiling showed that most lipids including cholesterol esters, ceramides, glycerides, fatty acids and phospholipids were decreased in TAC group and these alterations were reversed after HLJDD intervention. CONCLUSION: HLJDD alleviates TAC-induced pathological cardiac hypertrophy and remodeling, and its potential therapeutic mechanism involves the regulation of lipid metabolism.


Cardiomegaly/drug therapy , Cardiomegaly/metabolism , Cardiotonic Agents/pharmacology , Cardiotonic Agents/therapeutic use , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Animals , Atrial Remodeling/drug effects , Cardiomegaly/blood , Cardiomegaly/pathology , Disease Models, Animal , Fibrosis/drug therapy , Fibrosis/metabolism , Fibrosis/pathology , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Lipid Metabolism/drug effects , Lipidomics , Male , Metabolome/drug effects , Metabolomics , Mice, Inbred C57BL , NF-kappa B p50 Subunit/metabolism , Ventricular Remodeling/drug effects
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