Publications by authors named "Lihong Wang"

963 Publications

Photoacoustic Computed Tomography of Breast Cancer in Response to Neoadjuvant Chemotherapy.

Adv Sci (Weinh) 2021 04 23;8(7):2003396. Epub 2021 Feb 23.

Caltech Optical Imaging Laboratory Andrew and Peggy Cherng Department of Medical Engineering California Institute of Technology Pasadena CA 91125 USA.

Neoadjuvant chemotherapy (NAC) has contributed to improving breast cancer outcomes, and it would ideally reduce the need for definitive breast surgery in patients who have no residual cancer after NAC treatment. However, there is no reliable noninvasive imaging modality accepted as the routine method to assess response to NAC. Because of the inability to detect complete response, post-NAC surgery remains the standard of care. To overcome this limitation, a single-breath-hold photoacoustic computed tomography (SBH-PACT) system is developed to provide contrast similar to that of contrast-enhanced magnetic resonance imaging, but with much higher spatial and temporal resolution and without injection of contrast chemicals. SBH-PACT images breast cancer patients at three time points: before, during, and after NAC. The analysis of tumor size, blood vascular density, and irregularity in the distribution and morphology of the blood vessels on SBH-PACT accurately identifies response to NAC as confirmed by the histopathological diagnosis. SBH-PACT shows its near-term potential as a diagnostic tool for assessing breast cancer response to systemic treatment by noninvasively measuring the changes in cancer-associated angiogenesis. Further development of SBH-PACT may also enable serial imaging, rather than the use of current invasive biopsies, to diagnose and follow indeterminate breast lesions.
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http://dx.doi.org/10.1002/advs.202003396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025032PMC
April 2021

Snapshot photoacoustic topography through an ergodic relay of optical absorption in vivo.

Nat Protoc 2021 May 12;16(5):2381-2394. Epub 2021 Apr 12.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA.

Photoacoustic tomography (PAT) has demonstrated versatile biomedical applications, ranging from tracking single cells to monitoring whole-body dynamics of small animals and diagnosing human breast cancer. Currently, PAT has two major implementations: photoacoustic computed tomography (PACT) and photoacoustic microscopy (PAM). PACT uses a multi-element ultrasonic array for parallel detection, which is relatively complex and expensive. In contrast, PAM requires point-by-point scanning with a single-element detector, which has a limited imaging throughput. The trade-off between the system cost and throughput demands a new imaging method. To this end, we have developed photoacoustic topography through an ergodic relay (PATER). PATER can capture a wide-field image with only a single-element ultrasonic detector upon a single laser shot. This protocol describes the detailed procedures for PATER system construction, including component selection, equipment setup and system alignment. A step-by-step guide for in vivo imaging of a mouse brain is provided as an example application. Data acquisition, image reconstruction and troubleshooting procedures are also elaborated. It takes ~130 min to carry out this protocol, including ~60 min for both calibration and snapshot wide-field data acquisition using a laser with a 2-kHz pulse repetition rate. PATER offers low-cost snapshot wide-field imaging of fast dynamics, such as visualizing blood pulse wave propagation and tracking melanoma tumor cell circulation in mice in vivo. We envision that PATER will have wide biomedical applications and anticipate that the compact size of the setup will allow it to be further developed as a wearable device to monitor human vital signs.
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http://dx.doi.org/10.1038/s41596-020-00487-wDOI Listing
May 2021

Toward photoswitchable electronic pre-resonance stimulated Raman probes.

J Chem Phys 2021 Apr;154(13):135102

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Reversibly photoswitchable probes allow for a wide variety of optical imaging applications. In particular, photoswitchable fluorescent probes have significantly facilitated the development of super-resolution microscopy. Recently, stimulated Raman scattering (SRS) imaging, a sensitive and chemical-specific optical microscopy, has proven to be a powerful live-cell imaging strategy. Driven by the advances of newly developed Raman probes, in particular the pre-resonance enhanced narrow-band vibrational probes, electronic pre-resonance SRS (epr-SRS) has achieved super-multiplex imaging with sensitivity down to 250 nM and multiplexity up to 24 colors. However, despite the high demand, photoswitchable Raman probes have yet to be developed. Here, we propose a general strategy for devising photoswitchable epr-SRS probes. Toward this goal, we exploit the molecular electronic and vibrational coupling, in which we switch the electronic states of the molecules to four different states to turn their ground-state epr-SRS signals on and off. First, we showed that inducing transitions to both the electronic excited state and triplet state can effectively diminish the SRS peaks. Second, we revealed that the epr-SRS signals can be effectively switched off in red-absorbing organic molecules through light-facilitated transitions to a reduced state. Third, we identified that photoswitchable proteins with near-infrared photoswitchable absorbance, whose states are modulable with their electronic resonances detunable toward and away from the pump photon energy, can function as the photoswitchable epr-SRS probes with desirable sensitivity (<1 µM) and low photofatigue (>40 cycles). These photophysical characterizations and proof-of-concept demonstrations should advance the development of novel photoswitchable Raman probes and open up the unexplored Raman imaging capabilities.
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http://dx.doi.org/10.1063/5.0043791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019356PMC
April 2021

Multifocal photoacoustic microscopy using a single-element ultrasonic transducer through an ergodic relay.

Light Sci Appl 2020 Jul 31;9(1):135. Epub 2020 Jul 31.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA, 91125, USA.

Optical-resolution photoacoustic microscopy (OR-PAM) has demonstrated high-spatial-resolution imaging of optical absorption in biological tissue. To date, most OR-PAM systems rely on mechanical scanning with confocally aligned optical excitation and ultrasonic detection, limiting the wide-field imaging speed of these systems. Although several multifocal OR-PA (MFOR-PA) systems have attempted to address this limitation, they are hindered by the complex design in a constrained physical space. Here, we present a two-dimensional (2D) MFOR-PAM system that utilizes a 2D microlens array and an acoustic ergodic relay. Using a single-element ultrasonic transducer, this system can detect PA signals generated from 400 optical foci in parallel and then raster scan the optical foci patterns to form an MFOR-PAM image. This system improves the imaging resolution of an acoustic ergodic relay system from 220 to 13 μm and enables 400-folds shorter scanning time than that of a conventional OR-PAM system at the same resolution and laser repetition rate. We demonstrated the imaging ability of the system with both in vitro and in vivo experiments.
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http://dx.doi.org/10.1038/s41377-020-00372-xDOI Listing
July 2020

Characteristics of phytoplankton-zooplankton communities and the roles in the transmission of antibiotic resistance genes under the pressure of river contamination.

Sci Total Environ 2021 Mar 18;780:146452. Epub 2021 Mar 18.

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

Insight into the distribution of antibiotic resistance genes (ARGs) in phytoplankton-zooplankton communities (PZCs) is essential for the management and control of antibiotic resistance in aquatic ecosystems. This study characterized the profiles of PZCs and their carried ARGs in a typical urban river and ranked the factors (water physicochemical parameters, PZCs, bacterial abundance, and mobile genetic elements) influencing the dynamic of ARG profiles by the partial least squares path modeling. Results showed Cyanobacteria, Bacillariophyta and Chlorophyta were dominant phyla of phytoplankton, and Rotifera was with the highest abundance in zooplankton. River contamination markedly altered the structure of PZCs, increasing the abundance of phytoplankton and zooplankton, decreasing the diversity of phytoplankton while elevating in zooplankton. PZCs harbored large amounts of ARGs with average relative abundance of 2.35 × 10/copies nearly an order magnitude higher than the living water and most ARGs exhibited significant accumulation in PZCs with the aggravated environmental pollution. The partial least squares path modeling predicted the water parameters as the most important factor mainly playing indirect effects on ARGs via PZCs and bacterial communities, followed by mobile genetic elements as the most essential direct factor for ARGs profiles. Besides, PZCs were also important drivers for the carried ARGs via direct effects on the ARGs' composition and indirect effects on host bacterial communities of ARGs and their mobile genetic elements. The present study fills the gaps in knowledge about the distribution of ARGs in PZCs and provided a new perspective to decipher the key roles of PZCs in the maintenance and dissemination of ARGs in urban river ecosystems.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146452DOI Listing
March 2021

Structural brain changes and neuroticism in late-life depression: a neural basis for depression subtypes.

Int Psychogeriatr 2021 Mar 25:1-6. Epub 2021 Mar 25.

Department of Psychiatry, University of Connecticut, Farmington, CT, USA.

The neurobiological basis of neuroticism in late-life depression (LLD) is understudied. We hypothesized that older depressed subjects scoring high in measures of neuroticism would have smaller hippocampal and prefrontal volumes compared with non-neurotic older depressed subjects and with nondepressed comparison subjects based on previous research. Non-demented subjects were recruited and were either depressed with high neuroticism (n = 65), depressed with low neuroticism (n = 36), or never depressed (n = 27). For imaging outcomes focused on volumetric analyses, we found no significant between-group differences in hippocampal volume. However, we found several frontal lobe regions for which depressed subjects with high neuroticism scores had smaller volumes compared with non-neurotic older depressed subjects and with nondepressed comparison subjects, controlling for age and gender. These regions included the frontal pole, medial orbitofrontal cortex, and left pars orbitalis. In addition, we found that non-neurotic depressed subjects had a higher volume of non-white matter hypointensities on T1-weighted images (possibly related to cerebrovascular disease) than did neurotic depressed subjects. Our finding that depressed subjects low in neuroticism had higher volumes of non-white matter hypointensities is consistent with prior literature on "vascular depression." In contrast, the finding that those high in neuroticism had smaller frontal volume than depressed subjects low in neuroticism and never-depressed subjects highlight the importance of frontal circuitry in the subgroup of older depressed individuals with comorbid neuroticism. Together, these results implicate different neural mechanisms in older neurotic and non-neurotic depressed groups and suggest that multiple biological pathologies may lead to different clinical expressions of LLD.
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http://dx.doi.org/10.1017/S1041610221000284DOI Listing
March 2021

Molecular structures of nonvolatile components in the Haihong fruit wine and their free radical scavenging effect.

Food Chem 2021 Feb 16;353:129298. Epub 2021 Feb 16.

College of Special Education, Binzhou Medical University, Yantai 264003, PR China.

In order to investigate the correlation between free radical scavenging effect and the related molecular structures of active substances in the Haihong fruit (Malus Micromalus Makino) wine, sixteen kinds of components were isolated from the fruit wine. The structures of thirteen components were identified by UV, FTIR, LC-MS, 1D-NMR and 2D-NMR. The scavenging abilities of the fruit wine on DPPH (2,2-Diphenyl-1 -picrylhydrazyl radical), OH, O and the protective effects on red blood cell, SOD (Superoxide Dismutase), CAT(Catalase) and GPX(glutathione peroxidases) in aging mice tissues were studied. Results showed that the structures of o-diphenol and m-diphenol play an important role in scavenging free radicals. A larger conjugation system in functional molecule is conducive to getting a higher scavenging rate of free radicals. When the chemical shift of phenol hydrogen is lower, the anti-oxygenation ability is stronger. The fruit wine exhibits a strong scavenging ability on free radicals. It can inhibit the damage of red blood cells caused by OH radical.
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http://dx.doi.org/10.1016/j.foodchem.2021.129298DOI Listing
February 2021

Customizable Textile Sensors Based on Helical Core-Spun Yarns for Seamless Smart Garments.

Langmuir 2021 03 7;37(10):3122-3129. Epub 2021 Mar 7.

Research Center for Intelligent and Wearable Technology, College of Textiles and Clothing, State Key Laboratory of Bio-Fibers and Eco-Textiles, Intelligent Wearable Engineering Research Center of Qingdao, Qingdao University, Qingdao 266071, P. R. China.

Most of the current sensors cannot meet the needs for seamless integration into the textile substrates of smart clothing and require improvements in terms of comfort and durability. Herein, smart textile-based sensors that have different sensing properties with integrated electronic elements were fabricated by knitting graphene-based helical conductive core-spun yarns. Such graphene-modified core-spun yarns are employed as building blocks of textile strain sensors, which showed high elasticity (ε > 300%), fast response time (120 ms), excellent reproducibility (over 10 000 cycles), wide sensing range (up to 100% strain), and low detection limit (0.3% strain). Thus, resistance-type strain sensors and capacitance-type pressure sensors composed of graphene-based smart fabric could be used to monitor large-scale limb movement and subtle human physiological signals. Such seamless smart textile-based fabric composed of superelastic helical conductive core-spun yarns shows great potential for fabricating an intelligent device to achieve real-time precise medicine and healthcare.
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http://dx.doi.org/10.1021/acs.langmuir.0c03595DOI Listing
March 2021

Effects of physical exercise on the aging brain across imaging modalities: A meta-analysis of neuroimaging studies in randomized controlled trials.

Int J Geriatr Psychiatry 2021 Feb 16. Epub 2021 Feb 16.

Department of Psychiatry, University of Connecticut Health Center, Farmington, Connecticut, USA.

Background: Physical exercise is effective in protecting against age-related neurodegeneration and cognitive decline. Although there are many neuroimaging studies to evaluate the effect of physical exercise on aging brains, consistent conclusions are limited due to the wide variety of measuring techniques and small sample sizes.

Objective: Identify brain regions that show exercise-induced neuroplasticity consistently across various imaging modalities and correlate regional neuroplasticity with cognitive changes in older adults.

Methods: An electronic literature search for randomized controlled trials with magnetic resonance imaging measures was performed. We conducted a series of quantitative meta-analyses using activation likelihood estimation on included studies with voxel-based neuroimaging findings. Nonvoxelbased findings were summarized as a descriptive review.

Results: Out of 839 publications identified from the literature search, 30 experiments including 2670 participants from 22 papers met the criteria of meta-analyses. Overall, physical exercise consistently results in structural and functional changes in the hippocampus/parahippocampusl area and a cluster within the cerebellum. Although changes of medial/superior prefrontal cortex did not pass the stringent threshold, they were associated with cognitive changes.

Conclusions: This study highlights the effectiveness of physical exercise in inducing hippocampus plasticity, which may be crucially relevant for maintaining memory function in older adults.
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http://dx.doi.org/10.1002/gps.5510DOI Listing
February 2021

A Semi-Quantitative Risk Assessment and Management Strategies on COVID-19 Infection to Outpatient Health Care Workers in the Post-Pandemic Period.

Risk Manag Healthc Policy 2021 25;14:815-825. Epub 2021 Feb 25.

Hospital Infection Management Division, Xuan Wu Hospital Capital Medical University, Beijing, People's Republic of China.

Background: In the pandemic of COVID-19, due to asymptomatic patients and high personnel fluidity in outpatient clinics, health care workers (HCWs) in outpatients were facing severe threat from infection. There is an urgent need for a risk assessment to recognize and prevent infection risks.

Purpose: To establish a semi-quantitative risk assessment model on COVID-19 infections for HCWs in outpatient departments, and apply it to practices. Further to provide infection risk management strategies to reduce infection threats in the post-pandemic of COVID-19.

Methods: We used the method of Brainstorm, Literature study and Analytic Hierarchy Process (AHP) for risk factors selection and model construction, we also created corresponding indicators for each risk factors, in order to collect data in assessment practice.

Results: Eighteen risk factors were recognized and selected for model construction, by scatter plot, these risk factors had been classified into four parts, spanned the scopes of diagnosis and treatment, environment, personal protection and emergency handling, with specific management suggestions provided. In the practice, outpatient clinics were divided into three risk levels, 5 clinics in high risk level, 9 in medium risk level and 11 in low risk level.

Conclusion: A proper comprehensive risk assessment model for COVID-19 infections has been successfully established. With the model, the ability to COVID-19 prevention in outpatients can be easily evaluated. The strategies on disinfection, surveillance and personal protection were also valuable references in the post-pandemic of COVID-19.
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http://dx.doi.org/10.2147/RMHP.S293198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920612PMC
February 2021

Plantaginis Semen polysaccharides ameliorate renal damage through regulating NLRP3 inflammasome in gouty nephropathy rats.

Food Funct 2021 Mar 24;12(6):2543-2553. Epub 2021 Feb 24.

College of Pharmacy, Jiamusi University, Jiamusi, 154007, Heilongjiang, P.R. China.

Gouty nephropathy (GN) is considered to be a prevalent renal disease and is an inflammatory event mainly induced by MSU crystals. Plantaginis Semen is a traditional Chinese herb that has been used in the treatment of gout, gouty arthritis and GN, but the mechanism and ingredients have been unclear. In this study, we explored and evaluated the preliminary structural characterizations of Plantaginis Semen polysaccharides (PSPs) and the activity of protecting against renal damage in GN rats. Three polysaccharide fractions, PSP-D, PSP-H and PSP-S, were sequentially extracted by different processes from the seed of Plantago asiatica L. The Fourier transform infrared spectral (FTIR) results showed that there were significant differences between PSP-S and the other two polysaccharides (PSP-D and PSP-H). PSP-D and PSP-H have pyrene monomers and linkages of β-glycosides in their structures, and PSP-S has furanoside in the molecular structure. The scanning electron microscope (SEM) images of three polysaccharides showed that PSP-D has a smooth surface and a small curve, PSP-H is block-like and uneven in magnitude, whereas PSP-S is sea-tent-like and its surface is very distinct from the others. Main components and molar ratios are also different. Rats were randomly divided into six groups (n 8 per group): the control group, model group, positive group, and three treatment groups (PSP-D, PSP-H and PSP-S). For all groups except the control group, rats were intragastrically administered the adenine suspension (50 mg kg d) and fed with a high-yeast diet (15 g kg d) for 28 days. On the 9th day, the control group and the model group were administered normal saline at the same time. Treatment groups were individually given corresponding drugs for 20 days. We found that PSPs could prevent renal damage, including decreasing the inflammatory response and regulating the (NOD)-like receptor protein 3 (NLRP3) protein in renal tissue. The underlying mechanism was related to NLRP3 inflammasome signal pathways, and it could take effect through the down-regulation of the protein expression levels of NLRP3, ASC and caspase-1 and inhibit the release of downstream inflammatory factors. PSPs are promising polysaccharides that could protect against renal injury through ameliorating renal inflammation in GN rats. Plantaginis Semen polysaccharides are potential functional food ingredients or pharmacological agents for treating GN in clinical practice.
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http://dx.doi.org/10.1039/d0fo03143gDOI Listing
March 2021

A chloroplast heat shock protein modulates growth and abiotic stress response in creeping bentgrass.

Plant Cell Environ 2021 Feb 13. Epub 2021 Feb 13.

Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA.

Small heat shock proteins (sHSPs), a family of the ubiquitous stress proteins in plants acting as molecular chaperones to protect other proteins from stress-induced damage, have been implicated in plant growth and development as well as plant response to environmental stress, especially heat stress. In this study, a chloroplast-localized sHSP, AsHSP26.8, was overexpressed in creeping bentgrass (Agrostis stolonifera L.) to study its role in regulating plant growth and stress response. Transgenic (TG) creeping bentgrass plants displayed arrested root development, slow growth rate, twisted leaf blades and are more susceptible to heat and salt but less sensitive to drought stress compared to wild-type (WT) controls. RNA-seq analysis revealed that AsHSP26.8 modulated the expression of genes in auxin signalling and stress-related genes such as those encoding HSPs, heat shock factors and other transcription factors. Our results provide new evidence demonstrating that AsHSP26.8 negatively regulates plant growth and development and plays differential roles in plant response to a plethora of diverse abiotic stresses.
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http://dx.doi.org/10.1111/pce.14031DOI Listing
February 2021

Single-cell RNA-seq dissects the intratumoral heterogeneity of triple-negative breast cancer based on gene regulatory networks.

Mol Ther Nucleic Acids 2021 Mar 1;23:682-690. Epub 2021 Jan 1.

Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high intratumoral heterogeneity. Recent studies revealed that TNBC patients might comprise cells with distinct molecular subtypes. In addition, gene regulatory networks (GRNs) constructed based on single-cell RNA sequencing (scRNA-seq) data have demonstrated the significance for decoding the key regulators. We performed a comprehensive analysis of the GRNs for the intrinsic subtypes of TNBC patients using scRNA-seq. The copy number variations (CNVs) were inferred from scRNA-seq data and identified 545 malignant cells. The subtypes of the malignant cells were assigned based on the PAM50 model. The cell-cell communication analysis revealed that the macrophage plays a dominant role in the tumor microenvironment. Next, the GRN for each subtype was constructed through integrating gene co-expression and enrichment of transcription-binding motifs. Then, we identified the critical genes based on the centrality metrics of genes. Importantly, the critical gene 6 was ubiquitously upregulated in all subtypes, but it exerted diverse roles in each subtype through regulating different target genes. In conclusion, the construction of GRNs based on scRNA-seq data could help us to dissect the intratumoral heterogeneity and identify the critical genes of TNBC.
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http://dx.doi.org/10.1016/j.omtn.2020.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851423PMC
March 2021

Influence of Severe Gastrointestinal Complications in Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

Cancer Manag Res 2021 4;13:1041-1052. Epub 2021 Feb 4.

Department of Hematology, Peking University First Hospital, Beijing, 100034, People's Republic of China.

Background: This study assessed the clinical characteristics of gastrointestinal bleeding (GIB), obstruction (GIO), and perforation (GIP) in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) and the influence on long-term survival.

Methods: A retrospective analysis was performed of 148 patients with PGI-DLBCL admitted to Peking University First Hospital from August 1994 to May 2018. The clinical characteristics of GIB, GIO, and GIP before and after chemotherapy were recorded. The associated overall survival and progression-free survival were analyzed.

Results: Among 148 patients, 56.8% had gastrointestinal complications (GICs), including GIB, GIO, GIP, and multiple complications, and 22.6% of them occurred after chemotherapy, mostly during the first 4 cycles. The most common clinical manifestations of patients with GICs were abdominal pain or discomfort (79.8%), hematemesis or melena (22.6%), and abnormal bowel habits (17.9%). Patients with Eastern Cooperative Oncology Group (ECOG) score ≥2, tumor mass ≥10 cm, or intestinal involvement had significantly higher risk of severe GICs as initial manifestations. Among 130 patients who received chemotherapy, B symptoms, tumor mass ≥10 cm, and Lugano stage (IIE, IV) strongly correlated with GICs after chemotherapy ( < 0.05). Rituximab did not increase the risk of GICs. GICs which occurred before or after chemotherapy reduced the objective response rate at the end of chemotherapy. The prognosis of patients was significantly worsened by GIP, GIB, or multiple complications after chemotherapy ( < 0.05). GIB at presentation or GIO before or after chemotherapy had no prognostic value (both > 0.05).

Conclusion: GICs adversely affect the quality of life, prolong the length of hospitalization, and shorten the long-term survival of patients with PGI-DLBCL.
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http://dx.doi.org/10.2147/CMAR.S295671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869708PMC
February 2021

Biomimetic cytomembrane nanovaccines prevent breast cancer development in the long term.

Nanoscale 2021 Feb 10;13(6):3594-3601. Epub 2021 Feb 10.

Center Laboratory, Zhangjiagang Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu 215600, China.

Cytomembrane cancer nanovaccines are considered a promising approach to induce tumor-specific immunity. Most of the currently developed nanovaccines, unfortunately, fail to study the underlying mechanism for cancer prevention and therapy, as well as immune memory establishment, with their long-term anti-tumor immunity remaining unknown. Here, we present a strategy to prepare biomimetic cytomembrane nanovaccines (named CCMP@R837) consisting of antigenic cancer cell membrane (CCM)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with imiquimod (R@837) as an adjuvant to activate the immune system. We found that our CCMP@R837 system enhanced bone-marrow-derived dendritic cell uptake and maturation, as well as increased anti-tumor response against breast cancer 4T1 cells in vitro. Moreover, an immune memory was established after three-time immunization with CCMP@R837 in BALB/c mice. The CCMP@R837-immunized BALB/c mice exhibited suppressed tumor growth and a long survival period (75% of mice lived longer than 50 days after tumor formation). This long-term anti-tumor immunity was achieved by increasing CD8 T cells and decreasing regulatory T cells in the tumor while increasing effector memory T cells in the spleen. Overall, our platform demonstrates that CCMP@R837 can be a potential candidate for preventive cancer vaccines in the clinic.
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http://dx.doi.org/10.1039/d0nr08978hDOI Listing
February 2021

High-speed three-dimensional photoacoustic computed tomography for preclinical research and clinical translation.

Nat Commun 2021 02 9;12(1):882. Epub 2021 Feb 9.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA.

Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.
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http://dx.doi.org/10.1038/s41467-021-21232-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873071PMC
February 2021

Upregulated Expression of Toll-Like Receptor 7 in Peripheral Blood Basophils of Patients With Allergic Rhinitis.

Am J Rhinol Allergy 2021 Feb 8:1945892421993034. Epub 2021 Feb 8.

Department of Immunology, Translational Medicine Institute, Shenyang Medical College, Shenyang, China.

Background: Recently, it has been reported that Toll-like receptor 7 (TLR7) agonists can improve allergic rhinitis (AR) symptoms by up-regulation of Th1 cytokine release and suppression of Th2 cell functions. However, little is known of the expression of TLR7 in basophils of AR.

Objective: To explore the expression of TLR7 in basophils of AR, and influence of allergens on TLR7 expression.

Methods: The expression levels of TLR7 in basophils of patients with AR were determined by flow cytometry, and the influence of allergens on TLR7 expression was examined by real time (q) PCR.

Results: The percentages of TLR7CCR3 cells ( < 0.001 and  = 0.011), TLR7CD123HLA-DR cells ( = 0 .016 and  = 0.042) and TLR7CCR3CD123HLA-DR cells ( = 0.046 and  = 0.035) in blood granulocyte and mononucleated cell populations of the patients with AR were increased, respectively compared with HC subjects. TLR7 MFI on CCR3 cells ( = 0.050 and  = 0.043), CD123HLA-DR cells ( < 0.001 and  = 0.002) and CCR3CD123HLA-DR cells ( < 0.001 and  = 0.003) were enhanced compared with HC subjects. Allergens Der p1 and OVA provoked upregulation of TLR7 expression at both protein and mRNA levels and IL-13 production in KU812 cells. House Dust Mite extract (HDME), Artemisia sieversiana wild allergen extract (ASWE), IL-31, IL-33, IL-37, and TSLP provoked elevation of IL-6 release from KU812 cells following 2 h incubation period.

Conclusions: The percentage of TLR7 basophils and TLR7 expression intensity in a single basophil are both increased in the blood of patients with AR, indicating that basophils likely contribute to the pathogenesis of AR via TLR7.
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http://dx.doi.org/10.1177/1945892421993034DOI Listing
February 2021

Complexation of triangular silver(I) or copper(I) nitropyrazolates with dibenzothiophenes having potential use in adsorptive desulfurization.

Dalton Trans 2021 Mar;50(8):2915-2927

Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, China.

Triangular silver(i) and copper(i) 3,5-diethyl-4-nitropyrazolates (abbreviated as [Ag(denpz)]3 or Ag3pz3, and [Cu(denpz)]3 or Cu3pz3), as well as their adducts with dibenzothiophene (DBT), 4,6-dimethyldibenzothiophene (DMDBT) and benzothiophene (BT), have been prepared and characterized by a series of techniques. X-ray analyses show that these adducts are stabilized by MS, MC contacts and ππ stacking interactions. NMR measurements and theoretical calculations indicate that the intensity of interaction between the metal complexes and dibenzothiophenes follows the trend: Ag3pz3-DMDBT > Ag3pz3-DBT > Cu3pz3-DMDBT > Cu3pz3-DBT, which can be understood on the basis of a weak interaction between π-acid (Ag3pz3 or Cu3pz3) and π-base (DBT/DMDBT). Both complexes show good adsorptive ability and reusability toward the removal of DBT and DMDBT from model oil (n-octane), with the maximum adsorption capacity at room temperature being 39 mg S (DMDBT) per g Cu3pz3, 34 mg S (DMDBT) per g Ag3pz3, 40 mg S (DBT) per g Cu3pz3, 36 mg S (DBT) per g Ag3pz3, respectively. Compared to Ag3pz3, Cu3pz3 exhibits higher adsorptive capacities for DBT/DMDBT, which has been attributed to its lower molecular mass.
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http://dx.doi.org/10.1039/d0dt04037aDOI Listing
March 2021

MUC16 promotes EOC proliferation by regulating GLUT1 expression.

J Cell Mol Med 2021 Mar 4;25(6):3031-3040. Epub 2021 Feb 4.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

As a common malignancy in females with a higher incidence rate, epithelial ovarian cancer (EOC) is a heterogeneous disease with complexity and diversity in histology and therapeutic response. Although great progress has been made in diagnosis and therapeutic strategies, novel therapeutic strategies are required to improve survival. Although the promoting effect of mucin 16 (MUC16) on tumour progression has been reported, the potential mechanisms remain unclear. In our study, we reported that overexpression of MUC16 was significantly related to cell proliferation and disease progression in EOC. Results from clinical specimen analysis and cell experiment support this conclusion. Patients with a high MUC16 expression usually had a worse prognosis that those with a low expression. Cell proliferation ability was significantly decreased in EOC cell lines when the knockdown of MUC16. Further study shows that the function of MUC16 in cell proliferation is based on the regulation of glucose transporter 1 (GLUT1) expression. MUC16 can control glucose uptake by regulating GLUT1 in EOC cells, thereby promoting glycogen synthesis, so that tumour cells produce more energy for proliferation. This conclusion is based on two findings. First, the significant correlation between MUC16 and GLUT1 was verified by clinical specimen and TCGA data analysis. Then, alteration of MUC16 expression levels can affect the expression of GLUT1 and glucose uptake was also verified. Finally, this conclusion is further verified in vivo by tumour-bearing mice model. To summarize, our results suggest that MUC16 promotes EOC proliferation and disease progression by regulating GLUT1 expression.
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http://dx.doi.org/10.1111/jcmm.16345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957195PMC
March 2021

Real-time observation and control of optical chaos.

Sci Adv 2021 Jan 13;7(3). Epub 2021 Jan 13.

Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering and Department of Electrical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Optical chaotic system is a central research topic due to its scientific importance and practical relevance in key photonic applications such as laser optics and optical communication. Because of the ultrafast propagation of light, all previous studies on optical chaos are based on either static imaging or spectral measurement, which shows only time-averaged phenomena. The ability to reveal real-time optical chaotic dynamics and, hence, control its behavior is critical to the further understanding and engineering of these systems. Here, we report a real-time spatial-temporal imaging of an optical chaotic system, using compressed ultrafast photography. The time evolution of the system's phase map is imaged without repeating measurement. We also demonstrate the ability to simultaneously control and monitor optical chaotic systems in real time. Our work introduces a new angle to the study of nonrepeatable optical chaos, paving the way for fully understanding and using chaotic systems in various disciplines.
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http://dx.doi.org/10.1126/sciadv.abc8448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806228PMC
January 2021

LncRNA-Encoded Peptide: Functions and Predicting Methods.

Front Oncol 2020 14;10:622294. Epub 2021 Jan 14.

Department of Pathophysiology, Medical College of Southeast University, Nanjing, China.

Long non-coding RNA (lncRNA) was originally defined as the representative of the non-coding RNAs and unable to encode. However, recent reports suggest that some lncRNAs actually contain open reading frames that encode peptides. These coding products play important roles in the pathogenesis of many diseases. Here, we summarize the regulatory pathways of mammalian lncRNA-encoded peptides in influencing muscle function, mRNA stability, gene expression, and so on. We also address the promoting and inhibiting functions of the peptides in different cancers and other diseases. Then we introduce the computational predicting methods and data resources to predict the coding ability of lncRNA. The intention of this review is to provide references for further coding research and contribute to reveal the potential prospects for targeted tumor therapy.
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http://dx.doi.org/10.3389/fonc.2020.622294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842084PMC
January 2021

Analysis of the difference in pulse oxygen saturation between the ventral and dorsal fingers.

Int J Nurs Pract 2021 Jan 24:e12916. Epub 2021 Jan 24.

Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Aim: This study aimed to investigate the effect of different probe placements on the ventral and dorsal sides of the same finger using pulse oxygen saturation monitoring.

Methods: This clinical trial used a convenience sampling method in patients admitted to the Second Hospital of Hebei Medical University. We enrolled 1330 patients from March to July 2018, including patients who were hospitalized in the intensive care unit (n = 258) and in the general ward (n = 1072). Pulse oxygen saturation measurements obtained from the ventral and dorsal sides of the same finger were compared. This work adhered to the STROBE checklist requirements.

Results: We found that pulse oxygen saturation measurements between the dorsal and ventral sides of a finger were not affected by different fingers, disease types, the application of a ventilator, vasoactive drugs, the conscious state of the patient or the instrument model.

Conclusion: Our findings suggested no significant difference in saturation measurements with variation in the placement of the pulse oxygen saturation measurement instrument between the dorsal and ventral sides of a finger, regardless of illness severity. We believe that these results could simplify the monitoring procedures performed by nurses and eliminate worries concerning the inaccuracy of data because of varied probe positions.
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http://dx.doi.org/10.1111/ijn.12916DOI Listing
January 2021

C3 glomerulonephritis along with light chain proximal tubulopathy without crystal deposits in multiple myeloma: a case report.

World J Surg Oncol 2021 Jan 22;19(1):24. Epub 2021 Jan 22.

Department of Hematology, Peking University First Hospital, No.8 Xi Shi Ku Street, Xi ChengDistrict, Beijing, 100034, China.

Background: Multiple myeloma causes different types of renal injury. C3 glomerulonephritis (C3GN) is characterised by an abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of the complement system. While the association between C3GN and multiple myeloma has been well established, mild renal injury by C3GN in multiple myeloma patients with high levels of light chain has not been reported.

Case Presentation: A 55-year-old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy, and renal biopsy, he was diagnosed with IgA-type multiple myeloma accompanied by C3GN and light chain proximal tubulopathy without crystal deposits. Although he had a higher level of lambda serum-free light chain, the renal injury in this patient was mild. After treatment with four courses of BD, one course of PAD, and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function.

Conclusions: In multiple myeloma, the light chain reaches a certain level and persists, resulting in C3GN renal impairment. Early diagnosis and early intensive treatment are critical for the prognosis of such patients.
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http://dx.doi.org/10.1186/s12957-021-02135-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824921PMC
January 2021

Integration of Multitargeted Polymer-Based Contrast Agents with Photoacoustic Computed Tomography: An Imaging Technique to Visualize Breast Cancer Intratumor Heterogeneity.

ACS Nano 2021 02 19;15(2):2413-2427. Epub 2021 Jan 19.

Department of Chemistry & Biochemistry, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States.

One of the primary challenges in breast cancer diagnosis and treatment is intratumor heterogeneity (ITH), .., the coexistence of different genetically and epigenetically distinct malignant cells within the same tumor. Thus, the identification of ITH is critical for designing better treatments and hence to increase patient survival rates. Herein, we report a noninvasive hybrid imaging technology that integrates multitargeted and multiplexed patchy polymeric photoacoustic contrast agents (MTMPPPCAs) with single-impulse panoramic photoacoustic computed tomography (SIP-PACT). The target specificity ability of MTMPPPCAs to distinguish estrogen and progesterone receptor-positive breast tumors was demonstrated through both fluorescence and photoacoustic measurements and validated by tissue pathology analysis. This work provides the proof-of-concept of the MTMPPPCAs/SIP-PACT system to identify ITH in nonmetastatic tumors, with both high molecular specificity and real-time detection capability.
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http://dx.doi.org/10.1021/acsnano.0c05893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106867PMC
February 2021

Polyserositis as a primary clinical manifestation of CD7+ acute myelogenous leukemia with myeloid sarcoma: A case report.

Medicine (Baltimore) 2020 Dec;99(50):e23615

Department of Hematology, Peking University First Hospital, Peking University, Beijing, China.

Rationale: Myeloid sarcomas (MS) are defined as rare extramedullary masses composed of immature myeloid cells. MS mostly develops in patients with acute myeloid leukemia (AML), and involves primarily the skin, soft tissues, bones, and lymph nodes. Pleura and pericardium involvement of MS are extremely uncommon. Polyserositis is also a very rare extramedullary presentation of acute myeloid leukemia (AML).

Patient Concerns: A 30-year-old woman with a complaint of right neck mass combined with coughing for 2 months as well as fever and systemic edema for the last 10 days, was admitted to our center on July 11, 2019. Initial positron emission tomography (PET) scan indicated systemic lymphadenopathy, bilateral pleural effusion, and pericardial effusion.

Diagnosis: The initial pathological diagnosis of lymph nodes was MS. Subsequent bone marrow analysis confirmed AML.

Interventions: Conventional IA induction regimen followed by high-dose cytarabine (HiDAC) regimen.

Outcomes: Complete absorption of pericardial and pleural effusion after the first cycle of IA induction chemotherapy.

Lessons: Polyserositis can be an extramedullary presentation of AML. Patients with polyserositis should undergo routine flow cytometric analysis. For AML with extamedullary infiltration, systemic chemotherapy should be administered in all confirmed cases.
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http://dx.doi.org/10.1097/MD.0000000000023615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738120PMC
December 2020

Model to assess workload of village doctors in the National Essential Public Health Services Program in six provinces of China.

BMC Health Serv Res 2020 Dec 9;20(1):1134. Epub 2020 Dec 9.

Capital Institute of Pediatrics, 2 YaBao Road, #330, ChaoYang District, Beijing, 100020, China.

Background: No studies, particularly quantitative analyses, have been conducted regarding the workload of village doctors in the National Essential Public Health Services (NEPHS) program and differences in service delivery by village doctors, according to region and services. In this study, we developed a quantitative analysis approach to measure the workload of NEPHS provided by village doctors in six provinces of China in 2016. We aimed to identify areas and services of the NEPHS needing improvement, so as to implement targeted measures to ensure adequate delivery of NEPHSs in rural remote underserved areas.

Methods: Based on survey data from 300 town hospital centers (THCs) located in 60 counties in the six selected provinces, we calculated village doctors' share of workload under the NEPHS using the equivalent value (EV) model. To define the workload and corresponding EV of each NEPHS, a series of five meetings was held with THC managers, public health workers, family physicians, nurses and village doctors. Field observations were conducted to verify the workload and EV of each service.

Results: Village doctors' share of the workload under the NEPHS program was 43.71% across the 300 sampled THCs in six provinces. The village doctors' workload shares for different NEPHS ranged from 17.14 to 57.00%. The percentage workload undertaken by village doctors under the NEPHS program varied across different provinces, with the highest proportion 63.4% and the lowest 28.5%.

Conclusions: The total NEPHS workload assigned to village doctors by THCs in the six sampled provinces exceeded the Chinese government's requirement of 40%, but the workload proportion in some provinces was less than 40%. In addition, the percentage workload for some NEPHS undertaken by village doctors was lower than others. We suggest conducting district-level analysis of the workload among village doctors under the NEPHS program using the EV method, to identify areas and services needing improvement, to implement targeted measures to expand and promote health service provision in China's rural underserved areas.
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http://dx.doi.org/10.1186/s12913-020-05992-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727222PMC
December 2020

Combined inhibition of RNA polymerase I and mTORC1/2 synergize to combat oral squamous cell carcinoma.

Biomed Pharmacother 2021 Jan 13;133:110906. Epub 2020 Nov 13.

Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, Guangdong Province, China. Electronic address:

Oral squamous cell carcinoma (OSCC) is the major cause of morbidity and mortality in head and neck cancer patients worldwide. This malignant disease is challenging to treat because of the lack of effective curative strategies and the high incidence of recurrence. This study aimed to investigate the efficacy of a single and dual approach targeting ribosome biogenesis and protein translation to treat OSCC associated with the copy number variation (CNV) of ribosomal DNA (rDNA). Here, we found that primary OSCC tumors frequently exhibited a partial loss of 45S rDNA copy number and demonstrated a high susceptibility to CX5461 (a selective inhibitor of RNA polymerase I) and the coadministration of CX5461 and INK128 (a potent inhibitor of mTORC1/2). Combined treatment displayed the promising synergistic effects that induced cell apoptosis and reactive oxygen species (ROS) generation, and inhibited cell growth and proliferation. Moreover, INK128 compromised NHEJ-DNA repair pathway to reinforce the antitumor activity of CX5461. In vivo, the cotreatment synergistically suppressed tumor growth, triggered apoptosis and strikingly extended the survival time of tumor-bearing mice. Additionally, treatment with the individual compounds and coadministration appeared to reduce the incidence of enlarged inguinal lymph nodes. Our study supports that the combination of CX5461 and INK128 is a novel and efficacious therapeutic strategy that can combat this cancer and that 45S rDNA may serve as a useful indicator to predict the efficacy of this cotreatment.
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http://dx.doi.org/10.1016/j.biopha.2020.110906DOI Listing
January 2021

Cognitive variability, brain aging, and cognitive decline in late-life major depression.

Int J Geriatr Psychiatry 2021 05 2;36(5):665-676. Epub 2020 Dec 2.

Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut, USA.

Objectives: Older adults with late-life major depression (LLMD) are at increased risk of dementia. Dispersion, or within-person performance variability across cognitive tests, is a potential marker of cognitive decline. This study examined group differences in dispersion between LLMD and nondepressed healthy controls (HC) and investigated whether dispersion was a predictor of cognitive performance 1 year later in LLMD. We also explored demographic, clinical, and structural imaging correlates of dispersion in LLMD and HC. We hypothesized that dispersion would be greater in LLMD compared with HC and would be associated with worse cognitive performance 1 year later in LLMD.

Design: Participants were enrolled in the Neurobiology of Late-Life Depression, a naturalistic longitudinal investigation of the predictors of poor illness course in LLMD.

Participants: The baseline sample consisted of 121 older adults with LLMD and 39 HC; of these subjects, 94 LLMD and 35 HC underwent magnetic resonance imaging (MRI). One-year cognitive data were available for 107 LLMD patients.

Measurements: All participants underwent detailed clinical and structural MRI at baseline. LLMD participants also completed a comprehensive cognitive evaluation 1 year later.

Results: Higher test dispersion was evident in LLMD when compared with nondepressed controls. Greater baseline dispersion predicted 1-year cognitive decline in LLMD patients even when controlling for baseline cognitive functioning and demographic and clinical confounders. Dispersion was correlated with white matter lesions in LLMD but not HC. Dispersion was also correlated with anxiety in both LLMD and HC.

Conclusions: Dispersion is a marker of neurocognitive integrity that requires further exploration in LLMD.
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http://dx.doi.org/10.1002/gps.5465DOI Listing
May 2021

A nuclear transport-related gene signature combined with IDH mutation and 1p/19q codeletion better predicts the prognosis of glioma patients.

BMC Cancer 2020 Nov 9;20(1):1072. Epub 2020 Nov 9.

Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.

Background: The nuclear transport system has been proposed to be indispensable for cell proliferation and invasion in cancers. Prognostic biomarkers and molecular targets in nuclear transport systems have been developed. However, no systematic analysis of genes related to nuclear transport in gliomas has been performed. An integrated prognostic classification involving mutation and nuclear transport gene signatures has not yet been explored.

Methods: In the present study, we analyzed gliomas from a training cohort (TCGA dataset, n = 660) and validation cohort (CGGA dataset, n = 668) to develop a prognostic nuclear transport gene signature and generate an integrated classification system. Gene set enrichment analysis (GSEA) showed that glioblastoma (GBM) was mainly enriched in nuclear transport progress compared to lower-grade glioma (LGG). Then, we developed a nuclear transport risk score (NTRS) for gliomas with a training cohort. NTRS was significantly correlated with clinical and genetic characteristics, including grade, age, histology, IDH status and 1p/19q codeletion, in the training and validation cohorts.

Results: Survival analysis revealed that patients with a higher NTRS exhibited shorter overall survival. NTRS showed better prognostic value compared to classical molecular markers, including IDH status and 1p/19q codeletion. Furthermore, univariate and multivariate analyses indicated that NTRS was an independent prognostic factor for gliomas. Enrichment map and Gene Ontology analysis demonstrated that signaling pathways related to the cell cycle were enriched in the NTRS group. Subgroup survival analysis revealed that NTRS could differentiate the outcomes of low- and high-risk patients with wild-type IDH or mutant IDH and 1p/19q non-codeletion.

Conclusions: NTRS is associated with poor outcomes and could be an independent prognostic marker in diffuse gliomas. Prognostic classification combined with IDH mutation, 1p/19q codeletion and NTRS could better predict the survival of glioma patients.
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http://dx.doi.org/10.1186/s12885-020-07552-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654069PMC
November 2020