Publications by authors named "Kun Zhao"

517 Publications

Low-intensity pulsed ultrasound prevents angiotensin II-induced aortic smooth muscle cell phenotypic switch via hampering miR-17-5p and enhancing PPAR-γ.

Eur J Pharmacol 2021 Sep 20;911:174509. Epub 2021 Sep 20.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. Electronic address:

Vascular events can trigger a pathological phenotypic switch in vascular smooth muscle cells (VSMCs), decreasing and disrupting the plasticity and diversity of vascular networks. The development of novel therapeutic approaches is necessary to prevent these changes. We aimed to investigate the effects and associated mechanisms of low-intensity pulsed ultrasound (LIPUS) irradiation on the angiotensin II (AngII)-induced phenotypic switch in VSMCs. In vivo, AngII was infused subcutaneously for 4 weeks to stimulate vascular remodeling in mice, and LIPUS irradiation was applied for 20 min every 2 days for 4 weeks. In vitro, cultured rat aortic VSMCs (RAVSMCs) were pretreated once with LIPUS irradiation for 20 min before 48-h AngII stimulation. Our results showed that LIPUS irradiation prevents AngII-induced vascular remodeling of the whole wall artery without discriminating between adventitia and media in vivo and RAVSMC phenotypic switching in vitro. LIPUS irradiation downregulated miR-17-5p expression and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. The PPAR-γ activator rosiglitazone could mimic the favorable effects of LIPUS irradiation on AngII-treated RAVSMCs. In contrast, GW9662 could impede the LIPUS-mediated downregulation of RAVSMC proliferation and inflammation under AngII stimulation conditions in vivo and in vitro. Also, the miR-17-5p agomir has the same effects as GW9662 in vitro. Besides, the inhibitory effects of GW9662 against the anti-remodeling effects of LIPUS irradiation in AngII-induced RAVSMCs could be blocked by pretreatment with the miR-17-5p antagomir. Overall, LIPUS irradiation prevents AngII-induced RAVSMCs phenotypic switching through hampering miR-17-5p and enhancing PPAR-γ, suggesting a new approach for the treatment of vascular disorders.
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http://dx.doi.org/10.1016/j.ejphar.2021.174509DOI Listing
September 2021

α-Actinin1 promotes tumorigenesis and epithelial-mesenchymal transition of gastric cancer via the AKT/GSK3β/β-Catenin pathway.

Bioengineered 2021 12;12(1):5688-5704

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

α-Actinin1 (ACTN1), an actin cross-linking protein, is implicated in cytokinesis, cell adhesion, and cell migration. In addition, it is involved in the tumorigenesis and development of certain cancers, such as breast cancer. We explored the function of ACTN1 in gastric cancer (GC), which has largely remained unclear. High-throughput sequencing and public microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) revealed the upregulation of ACTN1 in gastric cancer with a poor prognosis. These results were further verified by western blotting (WB), Real-Time Quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry. We constructed loss and gain of function gastric cancer cells, which revealed the effect of ACTN1 over-expression on promoting GC cell proliferation, invasion, migration, and inhibited apoptosis. Mechanistic studies revealed that ACTN1 regulates the epithelial-mesenchymal transition (EMT) and tumorigenesis of gastric cancer via the AKT/GSK3β/β-catenin pathway, confirmed by the inhibitor of AKT MK2206. Altogether, these results demonstrated that ACTN1 could be a promising candidate for gastric cancer treatment.
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http://dx.doi.org/10.1080/21655979.2021.1967713DOI Listing
December 2021

Immunotherapy for lung cancer: Focusing on chimeric antigen receptor (CAR)-T cell therapy.

Curr Probl Cancer 2021 Sep 3:100791. Epub 2021 Sep 3.

Department of Radiation Oncology, Huaian Hospital of Huaian City, Huaian 223200, Huaian, Jiangsu, China. Electronic address:

Besides traditional treatment strategies, including surgery, radiotherapy, and chemotherapy for lung cancer as the leading cause of cancer incidence and death, immunotherapy has also emerged as a new treatment strategy. The goal of immunotherapy is to stimulate the immune system responses against cancer, using various approaches such as therapeutic vaccines, monoclonal antibodies, immune checkpoint inhibitors, and T-cell therapy. Chimeric antigen receptor (CAR)-T cells, one of the most popular cancer immunotherapy approaches in the last decade, are genetically engineered T-cells to redirect patients' immune responses to recognize and eliminate tumor-associated antigens (TAA)-expressing tumor cells. CAR-T cell therapy provides promising benefits in lung tumors. In this review, we summarize different immunotherapy approaches for lung cancer, the structure of CAR-T cells, currently undergoing CARs in clinical trials, and various TAAs are being investigated as potential targets in designing CAR-T cells for lung cancer.
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http://dx.doi.org/10.1016/j.currproblcancer.2021.100791DOI Listing
September 2021

Chromatin architecture reorganization during somatic cell reprogramming.

Curr Opin Genet Dev 2021 Sep 13;70:104-113. Epub 2021 Sep 13.

Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China. Electronic address:

It has been nearly 60 years since Dr John Gurdon achieved the first cloning of Xenopus by somatic cell nuclear transfer (SCNT). Later, in 2006, Takahashi and Yamanaka published their landmark study demonstrating the application of four transcription factors to induce pluripotency. These two amazing discoveries both clearly established that cell identity can be reprogrammed and that mature cells still contain the information required for lineage specification. Considering that different cell types possess identical genomes, what orchestrates reprogramming has attracted wide interest. Epigenetics, including high-level chromatin structure, might provide some answers. Benefitting from the tremendous progress in high-throughput and multi-omics techniques, we here address the roles and interactions of genome architecture, chromatin modifications, and transcription regulation during somatic cell reprogramming that were previously beyond reach. In addition, we provide perspectives on recent technical advances that might help to overcome certain barriers in the field.
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http://dx.doi.org/10.1016/j.gde.2021.07.006DOI Listing
September 2021

Chemiluminescence "signal-on-off" dual signals ratio biosensor based on single-stranded DNA functions as guy wires to detect EcoR V.

Talanta 2021 Dec 4;235:122749. Epub 2021 Aug 4.

College of Chemistry, Nanchang University, Nanchang, 330031, China. Electronic address:

Signal output mode is the important part of biosensor. In general, "signal on" and "signal off" are two common output modes. The development of dual signals-based ratio analysis as a powerful diagnostic tool has attracted widespread attention in the biosensor field in recent years. Dual signals ratio sensors with "signal on" and "signal off" are more favored because of their low background signal and better sensitivity and selectivity. In this study, inspired by the idea that EcoR V can cut specific sites of DNA to produce two corresponding fragments, and by using the capturing probe as guy wires, a reliable and sensitive method for EcoR V assay is developed based on the ratio of dual chemiluminescence (CL) signals for the first time. In particular, in the existence of the objective EcoR V, the substrate DNA would be degraded into two double stranded oligonucleotides with blunt ends which include the sequence I and the sequence II, then they can separately compete with two different corresponding capture probes on magnetic beads (MBs). One of capture probe hybridized with the sequence I containing more guanine (G) bases that reacted with the phenylglyoxal (PG) to produce chemical reaction which triggered a positive CL signal output I   as "signal-on"; another capture probe is priority to hybridize the sequence II, which triggered the weaker reporter DNA linked with horseradish peroxidase (HRP) probe to fall off the MBs, thereby outputting a negative CL signal I as "signal-off". By comparing the linear relation and the correlation coefficient, the I/I   ratio method has better linear relation (0.01-10 U/mL) and higher sensitivity (0.0045 U/mL). In addition, this developed strategy of high selectivity which can directly detect low concentration of target EcoR V in human serum, and thus this dual ratio biosensor might offer a promising detection approach for clinical diagnostics.
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http://dx.doi.org/10.1016/j.talanta.2021.122749DOI Listing
December 2021

Genetic prion disease-related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM.

Sci Adv 2021 Sep 8;7(37):eabg9676. Epub 2021 Sep 8.

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.

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http://dx.doi.org/10.1126/sciadv.abg9676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442898PMC
September 2021

A protocol for single-source dual-pulse stimulated emission depletion setup with Bessel modulation.

Microsc Res Tech 2021 Sep 6. Epub 2021 Sep 6.

Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, People's Republic of China.

STimulated Emission Depletion (STED) microscopy attains super-resolution in biological imaging beyond the diffraction limit. Here, we give a concise protocol to construct a dual-pulse STED setup with one super-continuum laser. Moreover, a flexible and dismountable Bessel modulation module is introduced for potential 2D-stack STED imaging. Experiments and notices are introduced in detail, with discussion on some important check-points for STED, such as detector saturation. Finally, the results validate the system working.
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http://dx.doi.org/10.1002/jemt.23922DOI Listing
September 2021

Efficacy and Safety of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Dermatology 2021 Aug 27:1-11. Epub 2021 Aug 27.

Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.

Background: Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives.

Objectives: To assess the efficacy and safety of JAK inhibitors for AD treatment.

Methods: We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator's Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI.

Results: We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25-3.56, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD -53.92, 95% CI -69.26 to -38.58, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10-1.42, p = 0.001).

Conclusion: Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.
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http://dx.doi.org/10.1159/000518541DOI Listing
August 2021

Percutaneous radiofrequency ablation near large vessels in beagle livers: the impact of time and distance on the ablation zone.

Int J Hyperthermia 2021 ;38(1):1263-1270

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.

Purpose: To investigate the effects of ablation time and distance between the radiofrequency ablation (RFA) electrode tip and a large vessel on the ablation zone in beagle livers.

Methods: Sixty-one percutaneous RFA coagulation zones were created near large vessels in 10 beagle livers . The ablated lesions were divided into four groups based on ablation time and distance between the electrode tip and a large vessel (group A, 3 min 0.5 cm; group B, 3 min 0 cm; group C, 5 min 0.5 cm; group D, 5 min 0 cm). The ablated area, long-axis diameters, short-axis diameters, and vessel wall injury were examined.

Results: With a fixed ablation time, the ablation zone created with the electrode tip at 0.5 cm from the large vessel was significantly larger than at 0 cm ( < .05). At a fixed distance between the electrode tip and vessel, the ablation zone created for 5 min was significantly larger than for 3 min ( < .05). The frequency of vessel wall injury in the 0 cm groups was significantly higher than that in the 0.5 cm groups (37.5% vs. 6.9%;  = .003, odds ratio, 7.43). The ratio of width to depth (Dw/Dz) was larger in the 0.5 cm groups than in the 0 cm groups ( < .001).

Conclusion: The ablation zone increased with longer ablation times and greater distances between the RFA tip and large vessels for perivascular lesions. The distance between the needle tip and blood vessels is an important factor that affects the overall ablation outcome.
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http://dx.doi.org/10.1080/02656736.2021.1966518DOI Listing
September 2021

Curvature-assisted self-assembly of Brownian squares on cylindrical surfaces.

J Colloid Interface Sci 2021 Jul 30;605:863-870. Epub 2021 Jul 30.

Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; Physics Department, Tianjin University, Tianjin 300072, PR China. Electronic address:

Hypothesis: We hypothesize that curved surfaces, including cylindrical surfaces, which go beyond prior experiments using flat surfaces, can significantly influence and alter the phase behavior and self-assembly of dense two-dimensional systems of Brownian colloids.

Experiments: Here, we report a first experimental study regarding the self-assembly of Brownian square platelets with an edge length L = 2.3 μm on cylindrical surfaces having different curvatures; these platelets are subjected to a depletion attraction in order to form a monolayer above the cylindrical surface, yet have nearly hard interactions within the monolayer. Simulations are also performed to confirm and explain the experimental observations.

Findings: Phase diagrams as a function of curvature are determined experimentally. Interestingly, hexagonal rotator crystal structures are observed for tubes having radii > 10.9L, but a tetratic phase is seen instead for the 10.9L tube at the corresponding platelet area fractions. We show that this transition is caused by the curvature-induced orientation-dependence of the depletion attraction between the squares and the underlying cylindrical surface. Brownian dynamics simulation results confirm the experimental observations and also illustrate helical structures formed by squares packing on cylinders. Our results demonstrate a way towards control over the self-assembly of anisotropic particles through curvature and depletion-attraction-induced orientational confinement.
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http://dx.doi.org/10.1016/j.jcis.2021.07.123DOI Listing
July 2021

Low-intensity pulsed ultrasound prevents prolonged hypoxia-induced cardiac fibrosis through HIF-1α/DNMT3a pathway via a TRAAK-dependent manner.

Clin Exp Pharmacol Physiol 2021 Aug 3. Epub 2021 Aug 3.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Hypoxia-induced cardiac fibrosis is an important pathological process in cardiovascular disorders. This study aimed to determine whether low-intensity pulsed ultrasound (LIPUS), a novel and safe apparatus, could alleviate hypoxia-induced cardiac fibrosis, and to elucidate the underlying mechanisms. Hypoxia (1% O ) and transverse aortic constriction (TAC) were performed on neonatal rat cardiac fibroblasts and mice to induce cardiac fibrosis, respectively. LIPUS irradiation was applied for 20 minutes every 6 hours for a total of 2 times in vitro, and every 2 days from 1 week before surgery to 4 weeks after surgery in vivo. We found that LIPUS dose-dependently attenuated hypoxia-induced cardiac fibroblast phenotypic conversion in vitro, and ameliorated TAC-induced cardiac fibrosis in vivo. Hypoxia significantly upregulated the nuclear protein expression of hypoxia-inducible factor-1α (HIF-1α) and DNA methyltransferase 3a (DNMT3a). LIPUS pre-treatment reversed the elevated expression of HIF-1α, and DNMT3a. Further experiments revealed that HIF-1α stabilizer dimethyloxalylglycine (DMOG) hindered the anti-fibrotic effect of LIPUS, and hampered LIPUS-mediated downregulation of DNMT3a. DNMT3a small interfering RNA (siRNA) prevented hypoxia-induced cardiac fibrosis. Results also showed that the mechanosensitive protein-TWIK-related arachidonic acid-activated K channel (TRAAK) messenger RNA (mRNA) expression was downregulated in hypoxia-induced cardiac fibroblasts, and TAC-induced hearts. TRAAK siRNA impeded LIPUS-mediated anti-fibrotic effect and downregulation of HIF-1α and DNMT3a. Above results indicated that LIPUS could prevent prolonged hypoxia-induced cardiac fibrosis through TRAAK-mediated HIF-1α/DNMT3a signalling pathway.
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http://dx.doi.org/10.1111/1440-1681.13562DOI Listing
August 2021

Genetic and clinical features of Chinese sporadic amyotrophic lateral sclerosis patients with TARDBP mutations.

Brain Behav 2021 08 1;11(8):e2312. Epub 2021 Aug 1.

Department of Neurology, First Medical Center, Chinese PLA General Hospital, Beijing, China.

Objectives: To investigate the genetic and clinical features of Chinese sporadic amyotrophic lateral sclerosis (SALS) patients with TARDBP mutations, we carried out a genetic analysis in a cohort of 391 SALS patients and explored the clinical manifestations of patients with TARDBP variants.

Materials And Methods: The coding region of all five coding exons of TARDBP, exons 2-6, were sequenced for mutations in 391 Chinese SALS patients. The clinical features of patients with TARDBP mutations were described and compared with cases in literatures.

Results: Two missense mutations in TARDBP gene, c.1132A > G (p.N378D) and c.1147A > G (p.I383V), were detected in three cases, showing a low frequency (0.77%, 3/391) of TARDBP missense mutations in Chinese SALS patients. Based on a retrospective analysis of literatures, p.N378D mutation mainly presents a phenotype of early onset, whereas p.I383V mutation presents pure ALS or ALS alongside semantic variant primary progressive aphasia (svPPA), a type of frontotemporal dementia (FTD).

Conclusions: Our results demonstrate that TARDBP mutation is a rare cause of Chinese SALS patients and expand the spectrum of phenotype. It is implied that genetic analysis of SALS patients plays a crucial role in uncovering the cause of disease, especially for cases developing early onset or alongside FTD.
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http://dx.doi.org/10.1002/brb3.2312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413724PMC
August 2021

Kiwifruit Genome Database (KGD): a comprehensive resource for kiwifruit genomics.

Hortic Res 2020 Aug 1;7(1):117. Epub 2020 Aug 1.

Boyce Thompson Institute, Cornell University, Ithaca, NY, 14853, USA.

Kiwifruit (Actinidia spp.) plants produce economically important fruits containing abundant, balanced phytonutrients with extraordinarily high vitamin C contents. Since the release of the first kiwifruit reference genome sequence in 2013, large volumes of genome and transcriptome data have been rapidly accumulated for a handful of kiwifruit species. To efficiently store, analyze, integrate, and disseminate these large-scale datasets to the research community, we constructed the Kiwifruit Genome Database (KGD; http://kiwifruitgenome.org/ ). The database currently contains all publicly available genome and gene sequences, gene annotations, biochemical pathways, transcriptome profiles derived from public RNA-Seq datasets, and comparative genomic analysis results such as syntenic blocks and homologous gene pairs between different kiwifruit genome assemblies. A set of user-friendly query interfaces, analysis tools and visualization modules have been implemented in KGD to facilitate translational and applied research in kiwifruit, which include JBrowse, a popular genome browser, and the NCBI BLAST sequence search tool. Other notable tools developed within KGD include a genome synteny viewer and tools for differential gene expression analysis as well as gene ontology (GO) term and pathway enrichment analysis.
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http://dx.doi.org/10.1038/s41438-020-0338-9DOI Listing
August 2020

Efficacy and Safety of Polyphenols for Osteoarthritis Treatment: a Meta-Analysis.

Clin Ther 2021 Jul 24. Epub 2021 Jul 24.

School of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, China. Electronic address:

Purpose: Osteoarthritis (OA) is a chronic and degenerative disorder associated with joint pain and loss of joint function. It is reported that polyphenols could yield articular benefits in patients with OA through the inhabitation of key inflammatory pathways. This meta-analysis was conducted to assess the efficacy and safety of polyphenol products for OA treatment.

Methods: This study included searches of PubMed, EMBASE, and the Cochrane Library databases from inception to November 6, 2019. Randomized controlled trials (RCTs) comparing polyphenols versus NSAIDs or placebo for human OA were included. Standardized mean differences (SMD) or risk ratios (RRs) were calculated for all relevant outcomes. Meta-analyses were conducted by using random effect models, and heterogeneity was assessed by using the I statistic.

Findings: A total of 18 RCTs (N = 1724) were eligible for analysis. Polyphenol products showed a significant advantage over placebo on pain relief (SMD, -1.11; 95% CI, -1.35 to -0.87) and functional improvement (SMD, -1.14; 95% CI, -1.38 to -0.90). No differences in safety outcomes were detected between polyphenols and placebo. There were no differences in efficacy outcomes between polyphenols and NSAIDs, although patients receiving polyphenols had a lower but nonsignificant risk of experiencing gastrointestinal dysfunction compared with those treated with NSAIDs. Polyphenols and NSAIDs in combination yielded more significant benefits in efficacy than NSAIDs alone.

Implications: The results of our study suggest that polyphenols may be a promising alternative for OA by relieving symptoms while reducing safety risks. However, the generalizability of our results may be limited by the quality and sample size of the available research, as well as the heterogeneity between RCTs. High-quality clinical trials are needed to make meaningful clinical practice recommendations.
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http://dx.doi.org/10.1016/j.clinthera.2021.06.005DOI Listing
July 2021

The Curvature Effect on the Diffusion of Single Brownian Squares on a Cylindrical Surface in the Presence of Depletion Attractions.

Langmuir 2021 Aug 19;37(30):9264-9268. Epub 2021 Jul 19.

Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.

The diffusion of single micron-sized Brownian square platelets on cylindrical surfaces with different radii of curvature in the presence of depletion attractions was studied experimentally by video microscopy. The translational motion of a square is found to be diffusive along the axial direction of the cylinder but sub-diffusive along the circumferential direction due to the confinement induced by gravity, while its rotational motion displays a sub-diffusive behavior due to the confinement induced by orientation-dependent depletion attractions. Such a confinement effect decreases as the radius of curvature increases and can be tuned both through surface curvatures and/or depletion attractions. Our work provides a new way to control the translational and rotational dynamics of anisotropic particles through curved surfaces in the presence of depletion attractions.
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http://dx.doi.org/10.1021/acs.langmuir.1c01540DOI Listing
August 2021

Discharge-Induced Enhancement of the Oxygen Evolution Reaction.

Angew Chem Int Ed Engl 2021 Sep 6;60(36):20042-20048. Epub 2021 Aug 6.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, P. R. China.

The fundamental understanding of the surface reconstruction induced by the applied potential is of great significance for enhancing the oxygen evolution reaction (OER). Here, we show that a previously overlooked discharge current in the low applied potential region also leads to in situ electrochemical activation of a nitrogen-doped nickel oxyhydroxide surface. We exploit the fact that doping of heteroatoms weakens the surface structure, and hence, a weak discharge current originating from the capacitive nature of nickel oxyhydroxide has a strong structure-reforming ability to promote the formation of nitrogen and oxygen vacancies. The current density at 1.4 V (vs. Hg/HgO) can dramatically increase by as much as 31.3 % after discharge in the low applied potential region. This work provides insight into in situ enhancement of the OER and suggests that the low applied potential region must be a primary consideration in evaluating the origin of the activity of electrocatalysts.
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http://dx.doi.org/10.1002/anie.202108770DOI Listing
September 2021

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome in Pterygium by MeRIP Sequencing.

Front Cell Dev Biol 2021 25;9:670528. Epub 2021 Jun 25.

Department of Ophthalmology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.

Aim: Pterygium is a common ocular surface disease, which is affected by a variety of factors. Invasion of the cornea can cause severe vision loss. N6-methyladenosine (m6A) is a common post-transcriptional modification of eukaryotic mRNA, which can regulate mRNA splicing, stability, nuclear transport, and translation. To our best knowledge, there is no current research on the mechanism of m6A in pterygium.

Methods: We obtained 24 pterygium tissues and 24 conjunctival tissues from each of 24 pterygium patients recruited from Shanghai Yangpu Hospital, and the level of m6A modification was detected using an m6A RNA Methylation Quantification Kit. Expression and location of , a key m6A methyltransferase, were identified by immunostaining. Then we used m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), RNA sequencing (RNA-seq), and bioinformatics analyses to compare the differential expression of m6A methylation in pterygium and normal conjunctival tissue.

Results: We identified 2,949 dysregulated m6A peaks in pterygium tissue, of which 2,145 were significantly upregulated and 804 were significantly downregulated. The altered m6A peak of genes were found to play a key role in the Hippo signaling pathway and endocytosis. Joint analyses of MeRIP-seq and RNA-seq data identified 72 hypermethylated m6A peaks and 15 hypomethylated m6A peaks in mRNA. After analyzing the differentially methylated m6A peaks and synchronously differentially expressed genes, we searched the Gene Expression Omnibus database and identified five genes related to the development of pterygium (, , , , and ).

Conclusion: Our research shows that m6A modification plays an important role in the development of pterygium and can be used as a potential new target for the treatment of pterygium in the future.
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http://dx.doi.org/10.3389/fcell.2021.670528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267473PMC
June 2021

Development and validation of a novel metabolic signature for predicting prognosis in patients with laryngeal cancer.

Eur Arch Otorhinolaryngol 2021 Sep 9;278(9):3585. Epub 2021 Jul 9.

Department of Radiology, The First Hospital of Qinhuangdao, Wenhua Road 258, Qinhuangdao, 066000, Hebei, China.

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http://dx.doi.org/10.1007/s00405-021-06984-2DOI Listing
September 2021

17-Estradiol Attenuates LPS-Induced Macrophage Inflammation In Vitro and Sepsis-Induced Vascular Inflammation In Vivo by Upregulating miR-29a-5p Expression.

Mediators Inflamm 2021 9;2021:9921897. Epub 2021 Jun 9.

Department of Urology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, Hebei 050000, China.

Excessive release of cytokines such as IL-1 and other inflammatory mediators synthesized and secreted by macrophages is the fundamental link of uncontrolled inflammatory response in sepsis. 17-Estradiol (E2) plays anti-inflammatory and vascular protective effects by regulating leukocyte infiltration and the expression of chemokines or cytokines induced by injury. However, the role of E2 in the inflammatory response of macrophages in sepsis and its mechanism are still not fully understood. In the present study, we show that E2 alleviates vascular inflammation in sepsis mice induced by cecal ligation puncture (CLP). E2 significantly decreases RAW 264.7 cell inflammation response by downregulating the expression of NLRP3. Furthermore, we found that miR-29a-5p was significantly downregulated in LPS-treated macrophages. Treating RAW 264.7 cells with E2 markedly upregulated the miR-29a-5p expression level. More importantly, we demonstrated that miR-29a-5p repressed NLRP3 expression by directly targeting its 3'-UTR. Loss- and gain-of-function experiments revealed that transfection of the miR-29a-5p mimic abrogates LPS-induced macrophage inflammation. Moreover, depletion of miR-29a-5p by its inhibitor largely promotes LPS-induced macrophage inflammation. In summary, miR-29a-5p upregulation induced by E2 alleviated RAW 264.7 cell inflammation response by aggravating miR-29a-5p repression of NLRP3 expression. E2 exerts significant anti-inflammatory efficacy in macrophages by regulating the miR-29a-5p/NLRP3 axis. Targeting miR-29a-5p may be a novel therapeutic strategy to suppress sepsis-induced vascular inflammation.
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http://dx.doi.org/10.1155/2021/9921897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211527PMC
June 2021

Crash landing of by MSHA pili-assisted braking and anchoring in a viscoelastic environment.

Elife 2021 07 2;10. Epub 2021 Jul 2.

Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.

Mannose-sensitive hemagglutinin (MSHA) pili and flagellum are critical for the surface attachment of , the first step of colonization on host surfaces. However, the cell landing mechanism remains largely unknown, particularly in viscoelastic environments such as the mucus layers of intestines. Here, combining the cysteine-substitution-based labeling method with single-cell tracking techniques, we quantitatively characterized the landing of by directly observing both pili and flagellum of cells in a viscoelastic non-Newtonian solution consisting of 2% Luria-Bertani and 1% methylcellulose (LB+MC). The results show that MSHA pili are evenly distributed along the cell length and can stick to surfaces at any point along the filament. With such properties, MSHA pili are observed to act as a brake and anchor during cell landing which includes three phases: running, lingering, and attaching. Importantly, loss of MSHA pili results in a more dramatic increase in mean path length in LB+MC than in 2% LB only or in 20% Ficoll solutions, indicating that the role of MSHA pili during cell landing is more apparent in viscoelastic non-Newtonian fluids than viscous Newtonian ones. Our work provides a detailed picture of the landing dynamics of under viscoelastic conditions, which can provide insights into ways to better control infections in a real mucus-like environment.
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http://dx.doi.org/10.7554/eLife.60655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282333PMC
July 2021

Engineering Active Micro and Nanomotors.

Micromachines (Basel) 2021 Jun 11;12(6). Epub 2021 Jun 11.

Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Micro- and nanomotors (MNMs) are micro/nanoparticles that can perform autonomous motion in complex fluids driven by different power sources. They have been attracting increasing attention due to their great potential in a variety of applications ranging from environmental science to biomedical engineering. Over the past decades, this field has evolved rapidly, with many significant innovations contributed by global researchers. In this review, we first briefly overview the methods used to propel motors and then present the main strategies used to design proper MNMs. Next, we highlight recent fascinating applications of MNMs in two examplary fields, water remediation and biomedical microrobots, and conclude this review with a brief discussion of challenges in the field.
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http://dx.doi.org/10.3390/mi12060687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231110PMC
June 2021

POM121 promotes proliferation and metastasis in non-small-cell lung cancer through TGF-β/SMAD and PI3K/AKT pathways.

Cancer Biomark 2021 Jun 12. Epub 2021 Jun 12.

Department of Oncology, Huaian Hospital of Huaian, Huaian, Jiangsu, China.

Background: Nuclear pore membrane protein 121 (POM121) is a novel biomarker involved in tumorigenesis and metastasis. However, little is known about the role of POM121 in non-small-cell lung cancer (NSCLC).

Objective: The aim of this study was to detect the expression of POM121 in NSCLC and its relationship with clinicopathologic feature and cell biological behavior, and explore the underlying mechanisms.

Methods: The expression of POM121 in NSCLC tissues and para-carcinoma tissues was compared by quantitative real-time PCR and immunohistochemistry analysis. The relationship between POM121 protein and clinicopathological characteristics in NSCLC was investigated. Roles of POM121 in NSCLC cells were investigated by CCK-8 assay, clone formation assay, transwell migration and invasion assay, and in vivo experiments. Variations of signaling pathways were determined by qRT-PCR and Western blot.

Results: The POM121 expression in NSCLC tissues was significantly higher than that in para-carcinoma tissues, both at the mRNA and protein level. The POM121 expression was related to sex, advanced differentiation, tumor diameter, lymph node metastases, distant metastases, American Joint Committee on Cancer (AJCC) stage, venous invasion, and perineural invasion in NSCLC. Kaplan-Meier analysis indicated that NSCLC patients with high POM121 expression had poor overall survival. Downregulation of POM121 inhibited cell proliferation, clone formation, migration and invasion. TGF-β/SMAD and PI3K/AKT pathways were involved in POM121-induced functional changes in NSCLC cells.

Conclusion: POM121 plays an oncogenic role in NSCLC through TGF-β/SMAD and PI3K/AKT pathways. POM121 expression is a potential independent prognostic factor for NSCLC.
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http://dx.doi.org/10.3233/CBM-210001DOI Listing
June 2021

Phosphorus doped nickel selenide for full device water splitting.

J Colloid Interface Sci 2021 Nov 10;602:115-122. Epub 2021 Jun 10.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, China. Electronic address:

The lack of high active and stable electrocatalysts has impeded the development of electrochemical water splitting device, which is promising technique for renewable energy conversion system. Here, we report a one-step protocol to synthesize P doped NiSe (P-NiSe) by selenylation process derived from nickel foam with assistant of NaHPO and Se powder. The P-NiSe could be directly used as working electrode and shows the superior electrochemical activity, offering current density of 10 mA cm with overpotential of 270 mV for OER and 71 mV for HER. The enhanced electrochemical activity can be ascribed to the P atom doping. The P atom doping leads to the high valence state of Ni active sites, which have high catalytic ability towards OER. Moreover, the P doping makes the d-band center of Ni atoms in P-NiSe move close to Fermi level, facilitating the HER kinetics with respect to proton adsorption and hydrogen desorption. When employed P-NiSe as both anodic and cathodic electrode in alkaline water electrolyzer, a current density of 10 mA cm can be achieved at 1.58 V. Our work highlights the importance of P doping in determining the surface electron configuration for full device water splitting and the facile synthesis protocol would be promising for realistic applications.
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http://dx.doi.org/10.1016/j.jcis.2021.06.013DOI Listing
November 2021

Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research?

Front Oncol 2021 19;11:630417. Epub 2021 May 19.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: NAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear.

Methods: In this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2.

Results: Compared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC.

Conclusion: NAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.
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http://dx.doi.org/10.3389/fonc.2021.630417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170476PMC
May 2021

KLK11 promotes the activation of mTOR and protein synthesis to facilitate cardiac hypertrophy.

BMC Cardiovasc Disord 2021 05 31;21(1):266. Epub 2021 May 31.

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

Background: Cardiovascular diseases have become the leading cause of death worldwide, and cardiac hypertrophy is the core mechanism underlying cardiac defect and heart failure. However, the underlying mechanisms of cardiac hypertrophy are not fully understood. Here we investigated the roles of Kallikrein 11 (KLK11) in cardiac hypertrophy.

Methods: Human and mouse hypertrophic heart tissues were used to determine the expression of KLK11 with quantitative real-time PCR and western blot. Mouse cardiac hypertrophy was induced by transverse aortic constriction (TAC), and cardiomyocyte hypertrophy was induced by angiotensin II. Cardiac function was analyzed by echocardiography. The signaling pathway was analyzed by western blot. Protein synthesis was monitored by the incorporation of [H]-leucine. Gene expression was analyzed by quantitative real-time PCR.

Results: The mRNA and protein levels of KLK11 were upregulated in human hypertrophic hearts. We also induced cardiac hypertrophy in mice and observed the upregulation of KLK11 in hypertrophic hearts. Our in vitro experiments demonstrated that KLK11 overexpression promoted whereas KLK11 knockdown repressed cardiomyocytes hypertrophy induced by angiotensin II, as evidenced by cardiomyocyte size and the expression of hypertrophy-related fetal genes. Besides, we knocked down KLK11 expression in mouse hearts with adeno-associated virus 9. Knockdown of KLK11 in mouse hearts inhibited TAC-induced decline in fraction shortening and ejection fraction, reduced the increase in heart weight, cardiomyocyte size, and expression of hypertrophic fetal genes. We also observed that KLK11 promoted protein synthesis, the key feature of cardiomyocyte hypertrophy, by regulating the pivotal machines S6K1 and 4EBP1. Mechanism study demonstrated that KLK11 promoted the activation of AKT-mTOR signaling to promote S6K1 and 4EBP1 pathway and protein synthesis. Repression of mTOR with rapamycin blocked the effects of KLK11 on S6K1 and 4EBP1 as well as protein synthesis. Besides, rapamycin treatment blocked the roles of KLK11 in the regulation of cardiomyocyte hypertrophy.

Conclusions: Our findings demonstrated that KLK11 promoted cardiomyocyte hypertrophy by activating AKT-mTOR signaling to promote protein synthesis.
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http://dx.doi.org/10.1186/s12872-021-02053-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167988PMC
May 2021

Real-time continuous measurement of intraoperative trace exhaled propofol by planar differential mobility spectrometry.

Anal Methods 2021 06 25;13(23):2624-2630. Epub 2021 May 25.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, People's Republic of China.

In order to study anesthetic pharmacokinetics and adequately adjust the anaesthesia depth of patients, real-time measurement of the intraoperative exhaled propofol concentration is of significant importance for anaesthetists. Although a series of analytical techniques and methods have been developed for the detection of exhaled propofol, differential mobility spectrometry (DMS) with the advantages of a much smaller instrument, faster response time and cheaper cost shows great potential for the point of care in the operating room. In this paper, a planar DMS was constructed for real-time continuous measurement of trace propofol in exhaled air. The effects of DMS parameters, such as the radio frequency voltage, the drift gas flow rate and the sampling flow rate of exhaled air on the propofol measurement under high humidity conditions were carefully investigated and discussed. Under the optimum experimental conditions, the limit of detection (LOD) for propofol was achieved in ppbv with a linear range of 0.5 to 25 ppbv, both of which meet clinical requirements. Finally, the planar DMS was performed on a patient undergoing thyroidectomy surgery to real-time monitor the intraoperative exhaled propofol, which demonstrated the capability of DMS for sensitive and breath-by-breath continuous measurement of intraoperative trace exhaled propofol.
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http://dx.doi.org/10.1039/d1ay00179eDOI Listing
June 2021

A simple and rapid method for fish sex identification based on recombinase-aided amplification and its use in Cynoglossus semilaevis.

Sci Rep 2021 05 17;11(1):10429. Epub 2021 May 17.

Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological Resources, College of Life Sciences, Anhui Normal University, Wuhu, 241000, China.

Fish sex identification is a basic technique of great importance for both fish genetic studies and fisheries. Due to the sexual reversal phenomenon in many fish species, a simple and rapid molecular identification method for fish genetic sex is urgently needed to suit versatile detection scenarios, such as point-of-need applications. In this study, we took Cynoglossus semilaevis as an example, established a recombinase-aided amplification (RAA)-based method for sex identification, and combined the RAA-detection with two result visualization approaches with distinct features, capillary electrophoresis (CE) and lateral flow dipstick (LFD). Specific primers and probe were designed to specifically detect the sex chromosome W of C. semilaevis in order to distinguish the genetic sex between males, pseudo-males and females. To evaluate the performance of our methods, the genetic sex for twenty-eight males, sixty-eight pseudo-males and fifty-four females were examined with the RAA-based method and classical PCR-based genotyping method, demonstrating the consistent results of sex identification between both methods. The RAA-LFD method is operationally simple, rapid (~ 30 min) and holds great potential for point-of-need applications of fish sex identification, including fishery fields. The method presented here could be effective for identifying fish gender with the ZW karyotype.
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http://dx.doi.org/10.1038/s41598-021-89571-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128863PMC
May 2021

Nitric Oxide Alleviated High Salt-Induced Cardiomyocyte Apoptosis and Autophagy Independent of Blood Pressure in Rats.

Front Cell Dev Biol 2021 29;9:646575. Epub 2021 Apr 29.

Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

The present study aimed to explore whether high-salt diet (HSD) could cause cardiac damage independent of blood pressure, and whether nitric oxide (NO) could alleviate high-salt-induced cardiomyocyte apoptosis and autophagy in rats. The rats received 8% HSD H9C2 cells or primary neonatal rat cardiomyocytes (NRCM) were treated with sodium chloride (NaCl) . The levels of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2, LC3 II/LC3 I, Beclin-1 and autophagy related 7 (ATG7) were increased in the heart of HSD rats with hypertension (HTN), and in hypertension-prone (HP) and hypertension-resistant (HR) rats. Middle and high doses (50 and 100 mM) of NaCl increased the level of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2, LC3 II/LC3 I, Beclin-1, and ATG7 in H9C2 cells and NRCM. The endothelial NO synthase (eNOS) level was increased, but p-eNOS level was reduced in the heart of HSD rats and H9C2 cells treated with 100 mM NaCl. The level of NO was reduced in the serum and heart of HSD rats. NO donor sodium nitroprusside (SNP) reversed the increases of cleaved-caspase 3/caspase 3, cleaved-caspase 8/caspase 8, Bax/Bcl2 induced by NaCl (100 mM) in H9C2 cells and NRCM. SNP treatment attenuated the increases of cleaved-caspase 3/caspase 3, Bax/Bcl2, LC3 II/LC3 I, Beclin-1, and ATG7 in the heart, but had no effect on the blood pressure of HSD rats with HR. These results demonstrated that HSD enhanced cardiac damage independently of blood pressure. Exogenous NO supplementarity could alleviate the high salt-induced apoptosis and autophagy in cardiomyocytes.
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http://dx.doi.org/10.3389/fcell.2021.646575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117152PMC
April 2021

Wild-type α-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding.

Proc Natl Acad Sci U S A 2021 May;118(20)

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201210, China;

Heterozygous point mutations of α-synuclein (α-syn) have been linked to the early onset and rapid progression of familial Parkinson's diseases (fPD). However, the interplay between hereditary mutant and wild-type (WT) α-syn and its role in the exacerbated pathology of α-syn in fPD progression are poorly understood. Here, we find that WT mice inoculated with the human E46K mutant α-syn fibril (hE46K) strain develop early-onset motor deficit and morphologically different α-syn aggregation compared with those inoculated with the human WT fibril (hWT) strain. By using cryo-electron microscopy, we reveal at the near-atomic level that the hE46K strain induces both human and mouse WT α-syn monomers to form the fibril structure of the hE46K strain. Moreover, the induced hWT strain inherits most of the pathological traits of the hE46K strain as well. Our work suggests that the structural and pathological features of mutant strains could be propagated by the WT α-syn in such a way that the mutant pathology would be amplified in fPD.
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http://dx.doi.org/10.1073/pnas.2012435118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158012PMC
May 2021

Noninvasive evaluation of ovarian endometriosis: a single-center experience.

Ann Palliat Med 2021 Apr;10(4):4728-4735

Department of Gynecological Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin, China.

Background: To investigate the relationships of cancer antigen (CA) 125, CA 19-9, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen (FIB), and D-dimer values with ovarian endometriosis (OEM), and to explore the validation of biomarkers for noninvasive preoperative evaluation of patients with severe OEM.

Methods: This retrospective case-control study included 413 women with OEM (of whom 143 cases were stage I to II, 139 cases were stage III, and 131 cases were stage IV, respectively) and 158 women without OEM as controls. Subjects' serum CA-125 and CA19-9 levels, and coagulation test results (serum PT, aPTT, and D-dimer values) were evaluated.

Results: The serum CA-125, aPTT, FIB and D-dimer levels were statistically different between OEM patients in the stages I to (and) II group and those in the stages III and IV group (P<0.05). However, a statistical difference in CA 19-9 levels and TT was only found between patients with stages III and IV OEM. In receiver operating characteristic (ROC) curve analysis of single indexes, the area under the ROC curve values for CA-125, CA19-9, aPTT, TT, FIB, and D-dimer were 0.953, 0.512, 0.66, 0.576, 0.573, and 0.624, respectively, for diagnosing stage III and stage IV OEM. In ROC curve analysis of combined indexes, the AUC values for aPTT + D-dimer, CA-125 + D-dimer, CA-125 + aPTT and CA-125 + D-dimer + aPTT were 0.672, 0.954, 0.958, and 0.961, respectively.

Conclusions: The combined index of CA-125, aPTT, and D-dimer is a valid noninvasive preoperative method for the evaluation of moderate and severe OEM, and may help to decrease the interval between the first complaint and a definitive diagnosis.
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http://dx.doi.org/10.21037/apm-21-481DOI Listing
April 2021
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