Publications by authors named "Shu Zhang"

1,832 Publications

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Modeling spatio-temporal patterns of holistic functional brain networks via multi-head guided attention graph neural networks (Multi-Head GAGNNs).

Med Image Anal 2022 Jun 15;80:102518. Epub 2022 Jun 15.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, #2006, Xiyuan Avenue, Chengdu, Sichuan 611731, China. Electronic address:

Mounting evidence has demonstrated that complex brain function processes are realized by the interaction of holistic functional brain networks which are spatially distributed across specific brain regions in a temporally dynamic fashion. Therefore, modeling spatio-temporal patterns of holistic functional brain networks plays an important role in understanding brain function. Compared to traditional modeling methods such as principal component analysis, independent component analysis, and sparse coding, superior performance has been achieved by recent deep learning methodologies. However, there are still two limitations of existing deep learning approaches for functional brain network modeling. They either (1) merely modeled a single targeted network and ignored holistic ones at one time, or (2) underutilized both spatial and temporal features of fMRI during network modeling, and the spatial/temporal accuracy was thus not warranted. To address these limitations, we proposed a novel Multi-Head Guided Attention Graph Neural Network (Multi-Head GAGNN) to simultaneously model both spatial and temporal patterns of holistic functional brain networks. Specifically, a spatial Multi-Head Attention Graph U-Net was first adopted to model the spatial patterns of multiple brain networks, and a temporal Multi-Head Guided Attention Network was then introduced to model the corresponding temporal patterns under the guidance of modeled spatial patterns. Based on seven task fMRI datasets from the public Human Connectome Project and resting state fMRI datasets from the public Autism Brain Imaging Data Exchange I of 1448 subjects, the proposed Multi-Head GAGNN showed superior ability and generalizability in modeling both spatial and temporal patterns of holistic functional brain networks in individual brains compared to other state-of-the-art (SOTA) models. Furthermore, the modeled spatio-temporal patterns of functional brain networks via the proposed Multi-Head GAGNN can better predict the individual cognitive behavioral measures compared to the other SOTA models. This study provided a novel and powerful tool for brain function modeling as well as for understanding the brain-cognitive behavior associations.
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http://dx.doi.org/10.1016/j.media.2022.102518DOI Listing
June 2022

Effect of Thermal Processing on the Metabolic Components of Black Beans on Ultra-High-Performance Liquid Chromatography Coupled with High-Field Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

Molecules 2022 Jun 18;27(12). Epub 2022 Jun 18.

College of Food, Heilongjiang Bayi Agricultural University, Xinfeng Lu 5, Daqing 163319, China.

An ultra-high-performance liquid chromatography coupled with high-field quadrupole-orbitrap mass spectrometry (UHPLC-QE-MS) histological platform was used to analyze the effects of two thermal processing methods (cooking and steaming) on the nutritional metabolic components of black beans. Black beans had the most amino acids, followed by lipids and polyphenols, and more sugars. Multivariate statistical analysis indicated that heat processing significantly affected the metabolic component content in black beans, with effects varying among different components. Polyphenols, especially flavonoids and isoflavones, were highly susceptible. A total of 197 and 210 differential metabolites were identified in both raw black beans and cooked and steamed black beans, respectively. Cooking reduced the cumulative content of amino acids, lipids, polyphenols, sugars, and nucleosides, whereas steaming reduced amino acid and lipid content, slightly increased polyphenol content, and significantly increased sugar and nucleoside content. Our results indicated that metabolic components were better retained during steaming than cooking. Heat treatment had the greatest impact on amino acids, followed by polyphenols, fatty acids, sugars, and vitamins, indicating that cooking promotes the transformation of most substances and the synthesis of a few. The results of this study provide a basis for further research and development of nutritional products using black beans.
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http://dx.doi.org/10.3390/molecules27123919DOI Listing
June 2022

Immune checkpoint inhibitors-associated cardiotoxicity in immunotherapy trials on gastrointestinal cancer patients.

Chin Med J (Engl) 2022 Apr 20;135(8):988-990. Epub 2022 Apr 20.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

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http://dx.doi.org/10.1097/CM9.0000000000002054DOI Listing
April 2022

Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.

Nat Commun 2022 Jun 17;13(1):3489. Epub 2022 Jun 17.

Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.
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http://dx.doi.org/10.1038/s41467-022-31126-5DOI Listing
June 2022

Aloperine Ameliorates IMQ-Induced Psoriasis by Attenuating Th17 Differentiation and Facilitating Their Conversion to Treg.

Front Pharmacol 2022 1;13:778755. Epub 2022 Jun 1.

NHC Key Laboratory of Respiratory Diseases, Department of Respiratory and Critical Care Medicine, The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

Aloperine is an anti-inflammatory compound isolated from the Chinese herb Previously, our group has reported that the generation of induced Treg was promoted by aloperine treatment in a mouse colitis model. However, the effect of aloperine on effector T cell subsets remains unclear. We therefore carefully examined the effect of aloperine on the differentiation of major subsets of T helper cells. Based on our results, psoriasis, a Th17 dominant skin disease, is selected to explore the potential therapeutic effect of aloperine . Herein, we demonstrated that topical application of aloperine suppressed epidermal proliferation, erythema, and infiltration of inflammatory cells in skin lesions. Mechanistic studies revealed that aloperine suppressed the differentiation of Th17 cells directly through inhibiting the phosphorylation of STAT3 or indirectly through impairing the secretion of Th17-promoting cytokines by dendritic cells. Moreover, aloperine enhanced the conversion of Th17 into Treg altering the pSTAT3/pSTAT5 ratio. Collectively, our study supported that aloperine possesses the capacity to affect Th17 differentiation and modulates Th17/Treg balance, thereby alleviating imiquimod (IMQ)-induced psoriasis in mice.
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http://dx.doi.org/10.3389/fphar.2022.778755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198605PMC
June 2022

Gyral peaks: Novel gyral landmarks in developing macaque brains.

Hum Brain Mapp 2022 Jun 17. Epub 2022 Jun 17.

School of Automation, Northwestern Polytechnical University, Xi'an, China.

Cerebral cortex development undergoes a variety of processes, which provide valuable information for the study of the developmental mechanism of cortical folding as well as its relationship to brain structural architectures and brain functions. Despite the variability in the anatomy-function relationship on the higher-order cortex, recent studies have succeeded in identifying typical cortical landmarks, such as sulcal pits, that bestow specific functional and cognitive patterns and remain invariant across subjects and ages with their invariance being related to a gene-mediated proto-map. Inspired by the success of these studies, we aim in this study at defining and identifying novel cortical landmarks, termed gyral peaks, which are the local highest foci on gyri. By analyzing data from 156 MRI scans of 32 macaque monkeys with the age spanned from 0 to 36 months, we identified 39 and 37 gyral peaks on the left and right hemispheres, respectively. Our investigation suggests that these gyral peaks are spatially consistent across individuals and relatively stable within the age range of this dataset. Moreover, compared with other gyri, gyral peaks have a thicker cortex, higher mean curvature, more pronounced hub-like features in structural connective networks, and are closer to the borders of structural connectivity-based cortical parcellations. The spatial distribution of gyral peaks was shown to correlate with that of other cortical landmarks, including sulcal pits. These results provide insights into the spatial arrangement and temporal development of gyral peaks as well as their relation to brain structure and function.
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http://dx.doi.org/10.1002/hbm.25971DOI Listing
June 2022

Disparities in positive results and dissemination of randomized controlled trials in immuno-oncology.

Int Rev Immunol 2022 Jun 17:1-10. Epub 2022 Jun 17.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: This cross-sectional and longitudinal analysis aimed to demonstrate the disparities in positive results and dissemination patterns of randomized controlled trials (RCTs) in global immuno-oncology (IO).

Methods: Phase II-IV RCTs with results reported by article publications registered on ClinicalTrials.gov in 2007-2018 studying immune checkpoint inhibitors (ICIs), adoptive cell transfer, cancer vaccines, and immune modulators were included.

Results: Twenty-eight percent of trials were positive (72 of 258), most of which were pharma-sponsored and focused on ICI and multiple IO therapies in lung cancer, melanoma, and multiple cancer types. The recent period of trial start year, upfront registration, large sample size, high strictness score on corticosteroid/infection-related criteria, and survival endpoints were associated with positive results. Trials from Mainland China had a faster publication timeline of positive results but lacked study diversity or full reporting of negative results compared with US and multinational trials. Compared with phase II trials, phase III-IV trials had a higher average proportion of positive results (28.9% vs. 22.2%) and a more stable change over the past decade (23.65% vs. 49.24%). Positive trials yielded more secondary manuscripts (10 vs. 4), a shorter publication process of approximately two years ( < 0.001), and a superiority in the dissemination of journals with an h-index >90 ( < 0.001) compared with negative trials.

Conclusion: Disparities in positive result dissemination are widespread in IO RCTs and affected by trial features. We proposed improvements in upfront registration, procedural integrity, and adequate inclusion of rival trials reporting negative results within the earlier two years in future reviews.
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http://dx.doi.org/10.1080/08830185.2022.2088744DOI Listing
June 2022

A single-step regression method based on transformer for retinal layer segmentation.

Phys Med Biol 2022 Jun 16. Epub 2022 Jun 16.

Shanghai Institute of Technology, Shanghai, Shanghai, 200235, CHINA.

The shape and structure of retinal layers are basic characteristics for the diagnosis of many ophthalmological diseases. Based on B-Scans of optical coherence tomography (OCT), most of retinal layer segmentation methods are composed of twosteps: classifying pixels and extracting retinal layers, in which the optimization of two independent steps decreases the accuracy. Although the methods based on deep learning are highly accurate, they require a large amount of labeled data. This paper proposes a single-step method based on Transformer for retinal layer segmentation, which is trained by axial data (A-Scans), to obtain the boundary of each layer. The proposed method was evaluated on two public data sets. The first one contains eight retinal layer boundaries for diabetic macular edema, and the second one contains nine retinal layer boundaries for healthy controls and subjects with multiple sclerosis. Its absolute average distance errors are 0.99 pixels and 3.67 pixels, respectively, for the two sets, and its root mean square error is 1.29 pixels for the latter set. In addition, its accuracy is acceptable even if the training data is reduced to 0.3. The proposed method achieves state-of-the-art performance while maintaining the correct topology and requires less labeled data.
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http://dx.doi.org/10.1088/1361-6560/ac799aDOI Listing
June 2022

SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis.

Proc Natl Acad Sci U S A 2022 Jun 14;119(26):e2122897119. Epub 2022 Jun 14.

Section of Infection and Immunity, Herman Ostrow School of Dentistry, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.
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http://dx.doi.org/10.1073/pnas.2122897119DOI Listing
June 2022

DNA methylation detection and site analysis by using an electrochemical biosensor constructed based on toehold-mediated strand displacement reaction.

Talanta 2022 Jun 2;249:123603. Epub 2022 Jun 2.

Department of Clinical and Military Laboratory Medicine, College of Medical Laboratory Science, Army Medical University, Chongqing, 400038, China. Electronic address:

DNA methylation has become a novel target for early diagnosis and prognosis of cancer as well as other related diseases. The accurate detection of the methylation sites of specific genes proved to be of great significance. However, the complex biological nature of clinical samples and the detection of low-abundance targets led to higher requirements for the testing technology. It has been found that by virtue of high sensitivity, rapid response, low cost, facile operation and applicability to microanalysis, electrochemical sensors have greatly contributed to the process of clinical diagnosis. In this study, a facile, rapid and highly sensitive electrochemical biosensor based on the peak current change was developed on the basis of high selectivity of toehold and greater efficiency of PNA strand displacement and used for the detection and site analysis of DNA methylation. Moreover, compared with non-methylated DNA sequences, methylated DNA sequences could be readily invaded by PNA probes, thereby resulting in the strand displacement and significant electrical signals. Therefore, methylation of cytosine sites was primarily analyzed based on electrical signals. Strand displacement by the target DNA sequences with different methylated sites can lead to substantial changes of strand displacement efficiency. As a result, the methylation sites can be analyzed on the basis of corresponding peak current response relation. This method has a detection limit of 0.075 pM and does not involve various complicated steps such as bisulfite treatment, enzyme digestion and PCR amplification. Indeed, one detection cycle can be completed in 60 min. The proposed technology might exhibit great potential in early clinical diagnosis and risk assessment of cancers and related diseases.
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http://dx.doi.org/10.1016/j.talanta.2022.123603DOI Listing
June 2022

Orf1B controls secretion of T3SS proteins and contributes to Edwardsiella piscicida adhesion to epithelial cells.

Vet Res 2022 Jun 13;53(1):40. Epub 2022 Jun 13.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, Hubei, China.

Edwardsiella piscicida is a Gram-negative enteric pathogen that causes hemorrhagic septicemia in fish. The type III secretion system (T3SS) is one of its two most important virulence islands. T3SS protein EseJ inhibits E. piscicida adhesion to epithelioma papillosum cyprini (EPC) cells by negatively regulating type 1 fimbria. Type 1 fimbria helps E. piscicida to adhere to fish epithelial cells. In this study, we characterized a functional unknown protein (Orf1B) encoded within the T3SS gene cluster of E. piscicida. This protein consists of 122 amino acids, sharing structural similarity with YscO in Vibrio parahaemolyticus. Orf1B controls secretion of T3SS translocon and effectors in E. piscicida. By immunoprecipitation, Orf1B was shown to interact with T3SS ATPase EsaN. This interaction may contribute to the assembly of the ATPase complex, which energizes the secretion of T3SS proteins. Moreover, disruption of Orf1B dramatically decreased E. piscicida adhesion to EPC cells due to the increased steady-state protein level of EseJ within E. piscicida. Taken together, this study partially unraveled the mechanisms through which Orf1B promotes secretion of T3SS proteins and contributes to E. piscicida adhesion. This study helps to improve our understanding on molecular mechanism of E. piscicida pathogenesis.
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http://dx.doi.org/10.1186/s13567-022-01057-6DOI Listing
June 2022

Current care practices for patients with Duchenne muscular dystrophy in China.

Brain Dev 2022 Jun 9. Epub 2022 Jun 9.

Research Center for Birth Defects Prevention and Control Technology, Chinese PLA General Hospital, 28 Fu-Xing Road, Beijing 100853, China. Electronic address:

Background: The coronavirus disease (COVID-19) pandemic has presented challenges in the care of patients with chronic diseases. We identified the challenges faced by Chinese patients with Duchenne muscular dystrophy (DMD) during the pandemic.

Methods: An online cross-sectional survey was conducted between March 27 and June 30, 2021.

Results: Of the 2105 valid questionnaire responses, 2,056 patients were from non-lockdown areas. In these areas, 42.8% reduced outside daily activities, 49.4% reduced rehabilitation service use, 39.7% postponed regular follow-ups, and 40.8% reported accelerated motor function decline. These figures generally increased for patients from lockdown areas-67.3% reduced outside daily activities, 44.9% reduced rehabilitation service use, 79.6% postponed regular follow-ups, and 55.1% reported accelerated motor function decline. Ambulation loss was most commonly reported in September and March before 2020; however, this trend was absent in 2020. Regarding the informed prices of disease-modifying drugs in Europe and the United States, 86.7% could afford a maximum of one-twentieth of the prices, 8.0% could afford one-tenth of the prices, and only 0.6% of the patients could afford the full prices.

Conclusions: Implementation of standardized care for DMD in China is consistent with global practices, and the COVID-19 pandemic has affected the care of patients with chronic diseases worldwide, particularly in lockdown areas. Telemedicine is an effective model for providing healthcare to such patients. Healthcare workers should assist patients and establish more robust chronic disease management systems. Collaboration between governmental and non-governmental entities could address the cost of disease-modifying drugs in China and other developing countries.
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http://dx.doi.org/10.1016/j.braindev.2022.05.007DOI Listing
June 2022

Machine learning algorithms for the rupture risk assessment in intracranial aneurysms: a diagnostic meta-analysis.

World Neurosurg 2022 Jun 8. Epub 2022 Jun 8.

Department of Neurosurgery, The First People's Hospital of Taicang, Taicang, Jiangsu, China. Electronic address:

Objective: Several machine learning algorithms have been increasingly applied to predict the rupture risk of intracranial aneurysms (IAs). We performed this diagnostic meta-analysis to comprehensively evaluate the diagnostic value of machine learning algorithms for assessing the rupture risk of IAs.

Methods: We systematically searched three electronic databases including Medline (via PubMed), the Cochrane Register of Controlled Trials (CENTRAL) (via OVID) and EMBASE (via Elseiver) to retrieve eligible studies from their inception through March 2021. The latest update was made in June 2021. StataMP version 14 was used to estimate all pooled diagnostic values.

Results: A total of 4 studies involving 6 reports were considered to meet the inclusion criteria finally. Our diagnostic meta-analysis generated the following pooled diagnostic values: sensitivity of 0.84 (95% confidence interval [CI], 0.75 to 0.90), specificity of 0.78 (95% CI, 0.68 to 0.85), positive likelihood ratio (PLR) of 3.8 (95% CI, 2.4 to 5.9), negative likelihood ratio (NLR) of 0.21 (95% CI, 0.12 to 0.35), diagnostic odd ratio (DOR) of 18 (95% CI, 7 to 46), and the area under the summary receiver operating characteristic curve (AUC) of 0.88 (95% CI, 0.85 to 0.90).

Conclusions: The result demonstrates that the diagnostic performance of machine learning algorithms for the rupture risk assessment of AIs was excellent. Considering the negative impact resulted from the limited number of eligible studies, we suggest developing more well-designed studies with large sample sizes to establish our finding.
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http://dx.doi.org/10.1016/j.wneu.2022.05.117DOI Listing
June 2022

Alkaloids from Alleviates DSS-Induced Ulcerative Colitis in Mice MAPK/NF-B/STAT3 Signaling Inhibition.

Evid Based Complement Alternat Med 2022 31;2022:6257778. Epub 2022 May 31.

Department of Pharmacy, Wuhan No. 1 Hospital (Wuhan Hospital of Traditional and Western Medicine), Wuhan 430022, China.

Fuzi ( Debx) has been traditionally used for the treatment of ulcerative colitis (UC) in China for thousands of years. The total alkaloids of (AAC) have been considered as the main medicinal components of fuzi, whereas its underlying anti-UC mechanisms remain elusive. In the present study, the dextran sulfate sodium (DSS)-induced UC mice model, which was consistent with the symptoms and pathological features of human UC, was established to comprehensively evaluate the anti-UC effects of AAC. The results indicated that AAC effectively improved the weight loss, disease activity index (DAI), spleen hyperplasia, and colon shortening, and thus alleviated the symptoms of UC mice. Meanwhile, AAC not only inhibited the MPO enzyme and the abnormal secretion of inflammatory cytokines (TNF-, IL-1, IL-6, IFN-, and IL-17A) and suppressed the overexpression of inflammatory mediators (TNF-, IL-1, and IL-6) of mRNA but also reduced the phosphorylation of p38 MAPK, ERK, and JNK, and the protein expressions of NF-B, IB-, STAT3, and JAK2 in the colon tissue. Furthermore, the LC-MS/MS quantitative determination suggested that the three low toxic monoester alkaloids were higher in both contents and proportion than that of the three high toxic diester alkaloids. Additionally, molecular docking was hired to investigate the interactions between alkaloid-receptor complexes, and it suggested the three monoester alkaloids exhibited higher binding affinities with the key target proteins of MAPK, NF-B, and STAT3. Our finding showcased the noteworthy anti-UC effects of AAC based on the MAPK/NF-B/STAT3 signaling pathway, which would provide practical and edge-cutting background information for the development and utilization of as a potential natural anti-UC remedy.
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http://dx.doi.org/10.1155/2022/6257778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173982PMC
May 2022

Light-activated photodeformable supramolecular dissipative self-assemblies.

Nat Commun 2022 Jun 9;13(1):3216. Epub 2022 Jun 9.

Institute of Advanced Materials, School of Chemistry and Chemical Engineering, and Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing, 211189, China.

Dissipative self-assembly, one of fundamentally important out-of-equilibrium self-assembly systems, can serve as a controllable platform to exhibit temporal processes for various non-stimulus responsive properties. However, construction of light-fueled dissipative self-assembly structures with transformable morphology to modulate non-photoresponsive properties remains a great challenge. Here, we report a light-activated photodeformable dissipative self-assembly system in aqueous solution as metastable fluorescent palette. Zwitterionic sulfonato-merocyanine is employed as a light-induced amphiphile to co-assemble with polyethyleneimine after light irradiation. The formed spherical nanoparticles spontaneously transform into cuboid ones in the dark with simultaneous variation of the particle sizes. Then the two kinds of nanoparticles can reversibly interconvert to each other by periodical light irradiation and thermal relaxation. Furthermore, after loading different fluorophores exhibiting red, green, blue emissions and their mixtures, all these fluorescent dissipative deformable nanoparticles display time-dependent fluorescence variation with wide range of colors. Owing to the excellent performance of photodeformable dissipative assembly platform, the light-controlled fluorescence has achieved a 358-fold enhancement. Therefore, exposing the nanoparticles loaded with fluorophores to light in a spatially controlled manner allows us to draw multicolored fluorescent images that spontaneously disappeared after a specific period of time.
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http://dx.doi.org/10.1038/s41467-022-30969-2DOI Listing
June 2022

A Novel DNA Repair Gene Signature for Immune Checkpoint Inhibitor-Based Therapy in Gastric Cancer.

Front Cell Dev Biol 2022 23;10:893546. Epub 2022 May 23.

Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients ( < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).
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http://dx.doi.org/10.3389/fcell.2022.893546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168368PMC
May 2022

Novel tissue-pressure sensing technology using a wide-band dielectric imaging system: An in vivo study.

J Cardiol 2022 May 31. Epub 2022 May 31.

Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Cardiovascular Institute, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China. Electronic address:

Background: A novel dielectric wide-band imaging system with tissue pressure (TP) technology provides real-time contact force (CF) monitoring using non-CF catheters. This study sought to investigate the feasibility, safety, and efficacy of ablation with TP technology.

Methods: Eighty-five patients with supraventricular tachycardia (SVT) were ablated with real-time monitoring of CF by TP technology and compared with 85 patients who underwent ablation with a conventional non-TP approach. Baseline characteristics, procedural data, and TP data were analyzed in the study. Ablation applications in the TP group were then subdivided into good contact and poor contact groups according to the TP level for analysis.

Results: The TP group had a significantly shorter procedural time (16.2 ± 6.9 min vs. 19.9 ± 10.0 min, p = 0.033), shorter ablation time (334.6 ± 166.9 s vs. 391.3 ± 195.7 s, p = 0.049), and fewer mean numbers of radiofrequency catheter ablation (RFCA) deliveries (6.2 ± 3.2 vs. 7.6 ± 5.2, p = 0.047) than the non-TP group. The achieved average percentage of TP >3 g was significantly higher in the good-contact group (97.94% vs. 15.48%, p < 0.001). The median impedance decreases during RFCA in the good contact group and poor contact group were 4.10 (0.30-6.88) Ω and 2.60 (-0.05-4.98) Ω at 10 s, 4.45 (0.58-8.25) Ω and 2.88 (0.23-5.70) Ω at 20 s, and 4.67 (1.95-9.08) Ω and 2.97 (-0.26-6.33) Ω at 30 s, respectively (p < 0.05 for comparisons between categories). All patients achieved acute success, and no complications were observed. Two patients in the TP group and one patient in the non-TP group experienced recurrence during follow-up.

Conclusion: TP-technology guided ablation of SVT is feasible, efficient, and safe.
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http://dx.doi.org/10.1016/j.jjcc.2022.05.004DOI Listing
May 2022

Drug discovery of sclerostin inhibitors.

Acta Pharm Sin B 2022 May 21;12(5):2150-2170. Epub 2022 Jan 21.

Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong 999077, China.

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.
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http://dx.doi.org/10.1016/j.apsb.2022.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136615PMC
May 2022

[Retracted] MicroRNA‑766 inhibits papillary thyroid cancer progression by directly targeting insulin receptor substrate 2 and regulating the PI3K/Akt pathway.

Int J Oncol 2022 Jul 1;61(1). Epub 2022 Jun 1.

Department of Breast and Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing the data from flow cytometry experiments in Figs. 2D, 4D and 5D, and certain of the tumor images featured in Fig. 7A, were strikingly similar to data appearing in different form in other articles by different authors. Furthermore, overlapping data panels were identified within this paper comparing the cell migration assay images between Figs. 2C and 4F. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to , the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 54: 315‑325, 2019; DOI: 10.3892/ijo.2018.4615].
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http://dx.doi.org/10.3892/ijo.2022.5376DOI Listing
July 2022

Japanese Diet and Mortality, Disability, and Dementia: Evidence from the Ohsaki Cohort Study.

Nutrients 2022 May 12;14(10). Epub 2022 May 12.

Division of Epidemiology, Department of Health Informatics and Public Health, Tohoku University School of Public Health, Graduate School of Medicine, Sendai 980-8575, Japan.

The Japanese dietary pattern has long been discussed as one of the factors behind the longevity of Japanese people. However, the health benefits of the Japanese dietary pattern have not been fully elucidated. We published the first report in the world regarding the relation between the Japanese dietary pattern and cardiovascular disease mortality in 2007 using cohort studies including Japanese residents of Ohsaki City, Miyagi Prefecture, Japan. Since then, we have developed the Japanese Diet Index (JDI) that was based on previous findings to assess the degree of the Japanese dietary pattern and to advance the evidence on the health effects of the Japanese dietary pattern. So far, we have explored the associations between the JDI score (in quartiles) and various outcomes. For all-cause mortality, in comparison to Q1 (the lowest), the multivariable hazard ratios (HRs) and 95% confidence intervals (95%CIs) were 0.92 (0.85-1.00) for Q2, 0.91 (0.83-0.99) for Q3, and 0.91 (0.83-0.99) for Q4 (the highest). For functional disability, the multivariable HRs (95%CIs) were 0.94 (0.81-1.09) for Q2, 0.90 (0.77-1.05) for Q3, and 0.79 (0.68-0.92) for Q4. For dementia, the multivariable HRs (95%CIs) were 0.88 (0.74-1.05) for Q2, 0.87 (0.73-1.04) for Q3, 0.79 (0.66-0.95) for Q4. In addition, people with higher adherence to the Japanese dietary pattern also showed decreases in disability and dementia risks. The purpose of this article was to review all six papers, summarize the health effects of the Japanese dietary pattern, and discuss implications for future research.
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http://dx.doi.org/10.3390/nu14102034DOI Listing
May 2022

How Does Leadership in Safety Management Affect Employees' Safety Performance? A Case Study from Mining Enterprises in China.

Int J Environ Res Public Health 2022 05 19;19(10). Epub 2022 May 19.

School of Resources and Safety Engineering, Central South University, Changsha 410083, China.

Leadership is a necessary element for ensuring workplace safety. Rather little is known about the role of leadership safety behaviours (LSBs) in the mining industry. Using regression analysis and structural equation modelling analysis, this study examined the cause-and-effect relationships between leadership safety behaviours and safety performance. Data were collected by questionnaires from 305 miners in China. Data were analysed using exploratory factor analysis and confirmatory factor analysis, which identified five main dimensions of LSBs: safety management commitment, safety communication with feedback, safety policy, safety incentives, and safety training; the analysis also identified three main dimensions of safety performance: employee's safety compliance, safety participation, and safety accidents. The results showed the overall effects of each LSB variable on safety compliance in descending order as: safety training (0.504), safety incentives (0.480), safety communication with feedback (0.377), safety management commitment (0.281), and safety policy (0.110). The overall effects of each LSB variable on safety participation in descending order were: safety training (0.706), safety incentives (0.496), safety management commitment (0.365), and safety policy (0.247). Furthermore, we found that safety management commitment and safety incentives increased employees' safety behaviours, but this influence was mediated by safety training, safety policy, and safety communication with feedback.
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http://dx.doi.org/10.3390/ijerph19106187DOI Listing
May 2022

Benzodiazepine-Based Sedation Did Not Add an Independent Risk of Delirium?

Crit Care Med 2022 06 19;50(6):e608-e609. Epub 2022 May 19.

Department of Anesthesiology and Translational Neuroscience Center, The Research Units of West China (2018RU012)-Chinese Academy of Medical Sciences, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1097/CCM.0000000000005515DOI Listing
June 2022

Chronic Obstructive Pulmonary Disease With Asthma-Like Features in the General Population in China.

Front Med (Lausanne) 2022 6;9:876240. Epub 2022 May 6.

State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.

Background: Patients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.

Methods: COPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV >15% and >400 ml after bronchodilator.

Results: COPD with concomitant features of asthma was found in 1.62% (95% CI 1.31-2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0-17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, < 0.001), and with a lower post-bronchodilator FEV%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.

Conclusions: COPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.
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http://dx.doi.org/10.3389/fmed.2022.876240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120624PMC
May 2022

Pyrolysis of furfural residues: Property and applications of the biochar.

J Environ Manage 2022 Aug 19;316:115324. Epub 2022 May 19.

School of Materials Science and Engineering, University of Jinan, Jinan, 250022, PR China. Electronic address:

Furfural residue (FR) is a solid waste generated during the production of furfural from corn cobs. The chemical energy and material potential of FR can be potentially recovered via pyrolysis. In this study, the pyrolysis of FR at the temperature ranging from 350 to 650 °C at the varied heating rate was investigated, aiming to understand the characteristics of the pyrolysis products. The results indicate that the organic components of FR tend to be cracked to form biochar and gases as the dominate products, due to the high ash content of FR. The FR-derived bio-oil also contained abundant organics derived from cellulose and lignin. Increasing pyrolysis temperature favored formation of the organics with fused ring structures. Lower heating rate in pyrolysis also formed biochar with higher thermal stability and higher fixed carbon content by enhancing the extent of deoxygenation. Additionally, the transformation of -OH via dehydration, -C-H into = C-H via dehydrogenation, and the cracking of CO during carbonization of biochar in the pyrolysis were also observed during pyrolysis of FR. Activation of the FR-derived biochar generated abundant micropores and mesopores, rendering the activated carbon with superior specific capacitance as electrodes of electrocapacitors (329 Fg) and the excellent adsorption efficiency of phosphate (up to 98.81%).
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http://dx.doi.org/10.1016/j.jenvman.2022.115324DOI Listing
August 2022

Spatial Distribution of Idiopathic Ventricular Arrhythmias Originating Around the Pulmonary Root: Lessons From Intracardiac Echocardiography.

JACC Clin Electrophysiol 2022 05 30;8(5):665-676. Epub 2022 Mar 30.

Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Cardiovascular Institute, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China.

Objectives: The purpose of this study was to investigate the spatial distribution of ventricular arrhythmias (VAs) and their relationship with anatomic landmarks in the right ventricular outflow tract (RVOT).

Background: Although controversy has mainly focused on whether VAs ablated in the RVOT originate above or below the pulmonary sinus, little is known about their actual distribution.

Methods: We performed mapping and ablation in the reconstructed RVOT using intracardiac echocardiography (ICE) and summarized the spatial electroanatomic characteristics of RVOT-VAs.

Results: A total of 50 VAs were recruited and were distributed among the 3 subregions: the pulmonary sinuses (19 of 50, 38%), sinus junctions (18 of 50, 36%), and infundibulum (13 of 50, 26%). In total, 70% (35 of 50) of ablation targets were within 10 mm (mean 4.3 ± 2.7 mm) of the pulmonary valve hinge point. An ablation target with both amplitude ≤1.14 mV and duration ≥101.5 milliseconds predicted an origin above the pulmonary sinus with a sensitivity of 84.2% and specificity of 84.4%. For the ablation targets (13 of 50, 26%) located in the infundibulum of the RVOT, 4 were surrounded by trabeculations, whereas only 1 ablation target in the sinus junction abutted the trabeculation (30.8% vs 5.6%).

Conclusions: Ablation targets of RVOT-VAs were mainly distributed around the hinge point of the pulmonary valve and the trabeculation of the infundibulum. ICE can clearly and precisely locate those anatomic landmarks of the RVOT.
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http://dx.doi.org/10.1016/j.jacep.2022.01.020DOI Listing
May 2022

Activation of waste paper: Influence of varied chemical agents on product properties.

Waste Manag 2022 Jun 16;146:94-105. Epub 2022 May 16.

School of Material Science and Engineering, University of Jinan, Jinan 250022, PR China. Electronic address:

Waste paper (WP) is rich in cellulose, which can be activated to produce porous carbon, bio-oil, and combustible gases. During chemical activation of WP, the use of varied chemical agents not only generates activated carbon of distinct pore structure but also bio-oil/gases of different property. In this study, the activation of WP with varied chemical agents was conducted. The distinct characteristics of activated carbon and also bio-oil/gases were correlated with the different nature of the used chemical agents. The results indicated that HPO and ZnCl catalyzed polymerization reactions for producing more bio-oil while less gases owing to their Brønsted and Lewis acidic sites. KCO showed high activity for cracking/gasification reactions, forming bio-oil with higher abundance of organics with smaller π-conjugated structures. In addition, ZnCl could create a very coarse porous structure with abundant macropores via destroying fiber structure in WP and promoting the growth of graphitic crystals. In comparison, KCO hindered the aromatization and facilitated the formation of amorphous activated carbon. KCO and ZnCl were much more effective than HPO for creating micropores and mesopores from WP, the derived activated carbon showed superior performances as the electrode of supercapacitor and adsorbent for adsorption of oxytetracycline from aqueous solution. In addition, KCO as activating agent showed lower environmental impact than ZnCl in terms of energy consumption, environmental pollution and the greenhouse effect.
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http://dx.doi.org/10.1016/j.wasman.2022.05.003DOI Listing
June 2022

Tumor-associated fibroblasts derived exosomes induce the proliferation and cisplatin resistance in esophageal squamous cell carcinoma cells through RIG-I/IFN-β signaling.

Bioengineered 2022 05;13(5):12462-12474

Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, Anhui, China.

Esophageal squamous cell carcinoma (ESCC) is a common type of malignant cancer. There is growing evidence suggesting that exosomes may participate in the cellular communication of tumor-associated fibroblasts (TAFs). However, the cisplatin resistance of TAF-derived exosomes to ESCC cells remains to be further studied. Exosomes were isolated from TAFs and characterized with Western blot and TEM assays. ESCC cell lines (TE-1 and KYSE-150) were incubated with TAFs-derived exosomes. To explore the biological function of TAF-derived exosomes in ESCC cell proliferation, apoptosis, and chemosensitivity, we conducted MTT assays and Flow Cytometry. The effects were also verified via Xenograft mice models. We found that TAFs-derived exosomes led to enhanced cell proliferation and reduced apoptosis of cells, accompanied by increased expression of RIG-I/IFN-β, and TAFs derived exosomes may affect the chemosensitivity to cisplatin via RIG-I/IFN-β signaling in ESCC. Taken together, ESCC cells could communicate with TAFs cells via TAFs-derived exosomes. Our findings might represent a novel mechanism involved in ESCC and may provide a potential biomarker for ESCC.
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http://dx.doi.org/10.1080/21655979.2022.2076008DOI Listing
May 2022

High dose chemoradiotherapy increases chance of organ preservation with satisfactory functional outcome for rectal cancer.

Radiat Oncol 2022 May 18;17(1):98. Epub 2022 May 18.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

Background: High dose chemoradiotherapy offers a curative chance for patients with rectal cancer that are unfit or unwilling to undergo surgical resection, yet its long-term survival and functional outcomes have been rarely investigated.

Methods: Patients with non-metastatic rectal adenocarcinoma who received pelvic radiation for curative intent from April 2006 to July 2017 were retrospectively investigated. Survival rates were analyzed using the Kaplan-Meier method. Quality of life and functional outcomes were evaluated using the EORTC quality of life questionnaire.

Results: A total of 57 patients were included, with a median age of 59.0 (range, 29-84) years. The numbers of patients who were diagnosed as stage I, II and III were 5 (8.8%), 16 (28.1%) and 36 (63.2%), respectively. 53 (93.0%) patients had tumor located within 5 cm from the anal verge. All patients received fluorouracil-based concurrent chemoradiotherapy with a median radiation dose of 80 (range, 60-86) Gy. All kinds of grade 3-4 adverse events occurred in 18 (31.6%) patients. 42 (73.7%) patients achieved a clinical complete response after chemoradiotherapy. After a median follow-up of 43.5 (range 14.9-163.2) months, 12 (21.1%) patients had local progression and 11 (19.3%) developed distant metastasis. The 3-year local recurrence-free survival and distant metastasis-free survival were 77.3% (95% CI, 65.7-88.8%) and 79.2% (95% CI, 68.2-90.2%), while the 3-year progression-free survival, cancer-specific survival, overall survival were 61.9% (95% CI, 48.8-75.0%), 93.1% (95% CI, 85.8-100.0%) and 91.4% (95% CI, 83.6-99.2%), respectively. For patients who had tumor located within 3 cm from the anal verge, the sphincter preservation rate was 85.3% at last follow-up. Long-term adverse events mainly were anal blood loss. 21 patients completed the quality-of-life questionnaire and had a score of the global health status of 78.57 ± 17.59. Of them, 95.2% reported no urinary incontinence and 85.7% reported no fecal incontinence.

Conclusions: High dose chemoradiation demonstrated promising survival outcomes with acceptable short-term and long-term side effects, and satisfying long-term functional outcomes and quality of life. It could be considered as a non-invasive alternative for rectal cancer patients who refuse surgery.
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http://dx.doi.org/10.1186/s13014-022-02066-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118735PMC
May 2022

Robotic laser position versus freehand in CT-guided percutaneous microwave ablation for single hepatocellular carcinoma (diameter < 3 cm): a preliminary study.

Int J Hyperthermia 2022 ;39(1):725-732

Department of Oncology, The People's Hospital of Jianyang City, Chengdu, China.

Purpose: To compare the accuracy and safety of robotic laser position (RLP) versus freehand for antenna CT-guided microwave ablation (MWA) of single hepatocellular carcinoma (HCC) (diameter < 3 cm).

Materials And Methods: This retrospective study was conducted between May 2020 and June 2021. A total of 40 patients with early HCC who underwent CT-guided MWA were divided into two groups: a freehand group ( = 20) and a RLP group ( = 20). Based on in-plane and out-of-plane data, the actual puncture point error (APPE), number of repositioning procedures, and operative duration were compared using the Mann-Whitney U test. Ablation-related complications were compared using the Chi-squared test.

Results: The mean diameter of HCC patients who received MWA was 2.4 ± 0.5 cm. For in-plane APPE, APPE was comparable between the two groups ( = 0.299). However, for the out-of-plane position, the APPE in the freehand group was higher than that in the RLP group ( = 0.027). The number of repositioning procedures was 0 (range, 0-0) for RLP-guided procedures and 3 (range, 2-5) for freehand procedures, showing a statistically significant difference between the two groups ( < 0.001). The mean operative duration for freehand procedures was 39 min, compared with 26 min for RLP-guided procedures, showing a significant difference ( = 0.013). No deaths or major complications were directly related to MWA. Minor complications in the freehand group were comparable with those in the RLP group ( = 0.313).

Conclusion: RLP guidance significantly reduces the number of antenna repositioning procedures in MWA and improves puncture accuracy for target HCC out-of-plane. In addition, the operative duration of robotic guidance was shorter than that of freehand guidance.
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http://dx.doi.org/10.1080/02656736.2022.2072526DOI Listing
May 2022

Publisher Correction: Single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma.

Nat Commun 2022 May 17;13(1):2848. Epub 2022 May 17.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, China.

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http://dx.doi.org/10.1038/s41467-022-30599-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114109PMC
May 2022
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