Publications by authors named "Xi Lei"

222 Publications

The Clinical Effect of a Combination of Mouse Nerve Growth Factor and Methylcobalamin to Treat Lumbar Disc Herniation with Foot Drop: A Retrospective Cohort Study.

Orthop Surg 2021 Jun 14. Epub 2021 Jun 14.

Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Objective: To investigate the clinical effect of mouse nerve growth factor (mNGF) and methylcobalamin (MeCbl) for the treatment of lumbar disk herniation (LDH) with foot drop.

Methods: A total of 46 patients suffering from LDH with foot drop who underwent transforaminal lumbar interbody fusion (TLIF) surgery in our department from January 2015 to December 2017 were retrospectively analyzed. We divided these patients into two groups according to the different postoperative treatment which independently selected by patients after signing informed consent form: one group of 25 patients was treated with MeCbl alone (Group MeCbl), the other group of 21 patients was treated with a combination of mNGF and MeCbl (Group MeCbl+mNGF). Patient demographics, the visual analogue scale (VAS) scores, sensory and muscular strength improvement statistics at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively were recorded. Motor/sensory deficits, sciatica and overall neurological outcome after treatment of MeCbl alone and combination of mNGF and MeCbl were retrospectively analyzed.

Results: The follow-up ranged between 12 and 42 months (mean 20.8 months). There were no significant differences between these two groups of patients with respect to sex ratio, age, smoking, diabetes, disease course, section of protruding disc(s), muscular strength of foot dorsiflexion or preoperative visual analogue scale (VAS) score (P > 0.05). The VAS scores of Group MeCbl+mNGF were significantly lower than Group MeCbl at 1 week, 4 weeks, 12 weeks, and 12 months postoperatively (4.32 ± 0.75 vs 5.25 ± 0.79,2.65 ± 0.48 vs 3.42 ± 0.52, 1.72 ± 0.36 vs 2.45 ± 0.39, 1.12 ± 0.22 vs 1.52 ± 0.24, P < 0.05). The effective rates of sensory improvement were significantly higher in Group MeCbl+mNGF compared with Group MeCbl at 12-week/12-month follow-up time point (90.48% vs 52.00%,95.24% vs 68.00%, P < 0.05). The effective rate of muscular strength improvement of the two groups did not differ significantly at 1 week after surgery but exhibited statistically significant differences at subsequent time points (61.90% vs 32.00%, 76.19% vs 44.00%, 80.95% vs 48.00%, P < 0.05).

Conclusions: Application of mNGF had clinical effects on promoting the recovery of neurological function in patients suffering from LDH with foot drop.
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http://dx.doi.org/10.1111/os.13014DOI Listing
June 2021

High-resolution in vivo imaging of rhesus cerebral cortex with ultrafast portable photoacoustic microscopy.

Neuroimage 2021 Jun 9;238:118260. Epub 2021 Jun 9.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China. Electronic address:

Revealing the structural and functional change of microvasculature is essential to match vascular response with neuronal activities in the investigation of neurovascular coupling. The increasing use of rhesus models in fundamental and clinical studies of neurovascular coupling presents an emerging need for a new imaging modality. Here we report a structural and functional cerebral vascular study of rhesus monkeys using an ultrafast, portable, and high resolution photoacoustic microscopic system with a long working distance and a special scanning mechanism to eliminate the relative displacement between the imaging interface and samples. We derived the structural and functional response of the cerebral vasculature to the alternating normoxic and hypoxic conditions by calculating the vascular diameter and functional connectivity. Both vasodilatation and vasoconstriction were observed in hypoxia. In addition to the change of vascular diameter, the decrease of functional connectivity is also an important phenomenon induced by the reduction of oxygen ventilatory. These results suggest that photoacoustic microscopy is a promising method to study the neurovascular coupling and cerebral vascular diseases due to the advanced features of high spatiotemporal resolution, excellent sensitivity to hemoglobin, and label-free imaging capability of observing hemodynamics.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118260DOI Listing
June 2021

A Multispectral Photoacoustic Tracking Strategy for Wide-Field and Real-Time Monitoring of Macrophages in Inflammation.

Anal Chem 2021 Jun 10;93(24):8467-8475. Epub 2021 Jun 10.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

Inflammation is a common defensive response of the vascular system that involves the activation and mediation of immune cell and stem cell homing. However, it is usually hard to track and analyze the real-time status of these cell types toward the inflammation microenvironment in a large field of view with desired resolution. Here, we designed and synthesized near-infrared absorbing semiconducting polymer nanoparticles, BBT-TQP-NP (BTNPs), as the cell tracker and utilized their photoacoustic activity to unveil the targeting behaviors of macrophages, neutrophils, and mesenchymal stem cells to the inflamed sites in mice. Facilitated by multispectral optical-resolution photoacoustic microscopy (ORPAM), we can continuously monitor the photoacoustic signals of the labeled cells with cellular resolution in a wide-field (a circle field-of-view with a diameter of 9 mm). In addition, the highly sensitive observation of vascular microstructures and labeled cells can reveal the time-dependent accumulating behaviors of various cell types toward inflammation sites. As a result, our study offers an effective and promising tracking strategy to analyze the status and fate of functional cells in targeting the diseased/damaged regions.
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http://dx.doi.org/10.1021/acs.analchem.1c00690DOI Listing
June 2021

Efficient and precise delivery of microRNA by photoacoustic force generated from semiconducting polymer-based nanocarriers.

Biomaterials 2021 May 24;275:120907. Epub 2021 May 24.

Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, 518055, China. Electronic address:

One major challenge in miRNA-based therapy is to explore facile delivery strategies, which can facilitate the efficient and precise accumulation of intrinsically instable microRNAs (miRNAs) at targeted tumor sites. To address this critical issue, for the first time we demonstrate that a near-infrared (NIR) pulse laser can guide efficient delivery of miRNAs mediated by a NIR-absorbing and photoacoustic active semiconducting polymer (SP) nanocarrier, which can generate photoacoustic radiation force to intravascularly overcome the endothelial barriers. Importantly, we demonstrate an ultrafast delivery of miRNA (miR-7) to tumor tissues under the irradiation of pulse laser in 20 min, showing a 5-fold boosted efficiency in comparison to the traditional passive targeting strategy. The delivered miR-7 acts as a sensitizer of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and synergizes with TRAIL-inducing compound (TIC), leading to sustained TRAIL upregulation for effective tumor suppression in mice. As such, our results indicate that the NIR-absorbing semiconducting polymer-mediated nanocarrier platform can significantly enhance the targeted delivery efficiency of therapeutic miRNAs to tumors, resulting in potent tumor growth inhibition.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120907DOI Listing
May 2021

In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.

Sci Rep 2021 Jun 3;11(1):11663. Epub 2021 Jun 3.

Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Canada.

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.
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http://dx.doi.org/10.1038/s41598-021-91165-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175443PMC
June 2021

Photoacoustic Force-Guided Precise and Fast Delivery of Nanomedicine with Boosted Therapeutic Efficacy.

Adv Sci (Weinh) 2021 Jun 3:e2100228. Epub 2021 Jun 3.

Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, 518055, China.

Precise and efficient delivery of nanomedicine to the target site has remained as a major roadblock in advanced cancer treatment. Here, a novel photoacoustic force (PAF)-guided nanotherapeutic system is reported based on a near-infrared (NIR)-absorbing semiconducting polymer (SP), showing significantly improved tumor accumulation and deep tissue penetration for enhanced phototherapeutic efficacy. The accumulation of nanoparticles in 4T1 tumor-bearing mice induced by the PAF strategy displays a fivefold enhancement in comparison with that of the traditional passive targeting pathway, in a significantly shortened time (45 min vs 24 h) with an enhanced penetration depth in tumors. Additionally, a tumor-bearing mouse model is rationally designed to unveil the mechanism, indicating that the nanoparticles enter solid tumors through enhanced transportation across blood vessel barriers via both inter-endothelial gaps and active trans-endothelial pathways. This process is specifically driven by PAF generated from the nanoparticles under NIR laser irradiation. The study thus demonstrates a new nanotherapeutic strategy with low dose, enhanced delivery efficiency in tumor, and boosted therapeutic efficacy, opening new doors for designing novel nanocarriers.
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http://dx.doi.org/10.1002/advs.202100228DOI Listing
June 2021

Infection microenvironment-activated nanoparticles for NIR-II photoacoustic imaging-guided photothermal/chemodynamic synergistic anti-infective therapy.

Biomaterials 2021 May 25;275:120918. Epub 2021 May 25.

Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, China. Electronic address:

Subcutaneous abscesses caused by drug-resistant bacteria pose huge challenges to human health. The design of infection microenvironment-activated biomaterials has an advantage for the diagnosis and treatment of infective diseases due to its high specificity and efficiency. Herein, a novel theranostic platform based on CuO nanoparticles (NPs) is successfully constructed via a simple, fast and low-cost approach. The CuO NPs exhibit high sensitivity to overexpressed HS and HO in the bacterial infection microenvironment. After in situ injection, the CuO NPs will rapidly react with the endogenous HS to generate CuS NPs, which exhibits high absorbance in the second near-infrared (NIR-II) biowindow. The CuS NPs serving as NIR-II photoacoustic contrast agents can exactly distinguish between inflammatory and normal tissues. With the guidance of NIR-II photoacoustic imaging (PAI), HS-activated photothermal antibacterial therapy (PTAT) can realize excellent antibacterial performance under 1060 nm laser irradiation. Meanwhile, the CuO NPs can effectively catalyze HO at the site of inflammation to produce hydroxyl radicals with strong antibacterial property via Fenton-like reaction, resulting in the damage of bacterial cell membrane. Furthermore, the application of CuO NPs can enhance epidermic migration and facilitate the re-epithelialization of the infected skin. In vivo experiment shows that 97.9% methicillin-resistant Staphylococcus aureus are eliminated by the synergistic PTAT and chemodynamic antibacterial therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120918DOI Listing
May 2021

On-Chip Multicolor Photoacoustic Imaging Flow Cytometry.

Anal Chem 2021 Jun 28;93(23):8134-8142. Epub 2021 May 28.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

On-chip imaging flow cytometry has been widely used in cancer biology, immunology, microbiology, and drug discovery. Pure optical imaging combined with flow cytometry to derive chemical, structural, and morphological features of cells provides systematic insights into biological processes. However, due to the high concentration and strong optical attenuation of red blood cells, preprocessing is necessary for optical flow cytometry while dealing with whole blood. In this study, we develop an on-chip photoacoustic imaging flow cytometry (PAIFC), which combines multicolor high-speed photoacoustic microscopy and microfluidics for cell imaging. The device employs a micro-optical scanner to achieve a miniaturized outer size of 30 × 17 × 24 mm and ultrafast cross-sectional imaging at a frame rate of 1758 Hz and provides lateral and axial resolutions of 2.2 and 33 μm, respectively. Using a multicolor strategy, PAIFC is able to differentiate cells labeled by external contrast agents, detect melanoma cells with an endogenous contrast in whole blood, and image melanoma cells in blood samples from tumor-bearing mice. The results suggest that PAIFC has sufficient sensitivity and specificity for future cell-on-chip applications.
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http://dx.doi.org/10.1021/acs.analchem.0c05218DOI Listing
June 2021

Chronic cranial window for photoacoustic imaging: a mini review.

Vis Comput Ind Biomed Art 2021 May 26;4(1):15. Epub 2021 May 26.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China.

Photoacoustic (PA) microscopy is being increasingly used to visualize the microcirculation of the brain cortex at the micron level in living rodents. By combining it with long-term cranial window techniques, vasculature can be monitored over a period of days extending to months through a field of view. To fulfill the requirements of long-term in vivo PA imaging, the cranial window must involve a simple and rapid surgical procedure, biological compatibility, and sufficient optical-acoustic transparency, which are major challenges. Recently, several cranial window techniques have been reported for longitudinal PA imaging. Here, the development of chronic cranial windows for PA imaging is reviewed and its technical details are discussed, including window installation, imaging quality, and longitudinal stability.
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http://dx.doi.org/10.1186/s42492-021-00081-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155166PMC
May 2021

One-for-all phototheranostics: Single component AIE dots as multi-modality theranostic agent for fluorescence-photoacoustic imaging-guided synergistic cancer therapy.

Biomaterials 2021 07 11;274:120892. Epub 2021 May 11.

Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, 999077, Hong Kong, China. Electronic address:

Construction of single component theranostic agent with one-for-all features to concurrently afford both multi-modality imaging and therapy is an appealing yet significantly challenging task. Herein, a type of luminogens with aggregation-induced emission (AIE) characteristics are tactfully designed and facilely synthesized. These AIE luminogens (AIEgens) exhibit long emission wavelengths, good photostability, remarkable biocompatibility, good reactive oxygen species (ROS) generation performance and excellent photothermal conversion efficiency, which allow them to be powerfully utilized for in vitro and in vivo cancer phototheranostics. The results show that one of the AIEgens is capable of precisely diagnosing solid tumors of mice by means of combined near-infrared-I/II (NIR-I/II) fluorescence-photoacoustic imaging, meanwhile this AIEgen can activate photodynamic and photothermal synergistic therapy (PDT-PTT) upon laser irradiation, resulting in excellent tumor elimination efficacy with only once injection and irradiation. This study thus provides a versatile platform for practical cancer theranostics.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120892DOI Listing
July 2021

Differential Mutation Detection Capability Through Capture-Based Targeted Sequencing in Plasma Samples in Hepatocellular Carcinoma.

Front Oncol 2021 30;11:596789. Epub 2021 Apr 30.

Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing (Army Medical University), Chongqing, China.

Circulating tumor DNA (ctDNA) is a promising biomarker for accurate monitoring and less invasive assessment of tumor burden and treatment response. Here, targeted next-generation sequencing (NGS) with a designed gene panel of 176 cancer-relevant genes was used to assess mutations in 90 ctDNA samples from 90 patients with multiple types of liver disease and 10 healthy donor samples for control. Using our ctDNA detection panel, we identified mutations in 98.89% (89/90) of patient plasma biopsy samples, and 19 coding variants located in 10 cancer-related genes [, adhesion G protein-coupled receptor (), , and ] were identified in 96.7% of patients (87/90). The 10 top mutated genes were tumor protein p53 (), , titin (), , and . and and and mutations tended to occur together in hepatocellular carcinoma samples. Most importantly, we found that most of those variants were insertions (frameshift insertions) and deletions (frameshift deletions and in-frame deletions), such as insertion variants in , and ; such mutations were detected in almost 95% of patients. Our study demonstrated that the targeted NGS-based ctDNA mutation profiling was a useful tool for hepatocellular carcinoma (HCC) monitoring and could potentially be used to guide treatment decisions in HCC.
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http://dx.doi.org/10.3389/fonc.2021.596789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120297PMC
April 2021

Prognostic value of ferroptosis-related genes in patients with lung adenocarcinoma.

Thorac Cancer 2021 Jun 12;12(12):1890-1899. Epub 2021 May 12.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: The prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron-dependent regulatory cell death. It is still unclear whether the expression of ferroptosis-related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD.

Methods: We retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high- and low-risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors.

Results: Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune-related pathways and immune infiltration differences between high- and low-risk groups. A prognostic model integrating 10 ferroptosis-related genes (FR-DEGs), and clinical factors were constructed and validated in an external cohort.

Conclusions: The FR-DEGs signature was related to immune infiltration, and a model based on FR-DEGs and clinical factors was established to predict the prognosis of patients with LUAD.
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http://dx.doi.org/10.1111/1759-7714.13998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201541PMC
June 2021

Role of phosphodiesterase 1 in the pathophysiology of diseases and potential therapeutic opportunities.

Pharmacol Ther 2021 Apr 22;226:107858. Epub 2021 Apr 22.

Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA 23298-0204, USA. Electronic address:

Cyclic nucleotide phosphodiesterases (PDEs) are superfamily of enzymes that regulate the spatial and temporal relationship of second messenger signaling in the cellular system. Among the 11 different families of PDEs, phosphodiesterase 1 (PDE1) sub-family of enzymes hydrolyze both 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) in a mutually competitive manner. The catalytic activity of PDE1 is stimulated by their binding to Ca/calmodulin (CaM), resulting in the integration of Ca and cyclic nucleotide-mediated signaling in various diseases. The PDE1 family includes three subtypes, PDE1A, PDE1B and PDE1C, which differ for their relative affinities for cAMP and cGMP. These isoforms are differentially expressed throughout the body, including the cardiovascular, central nervous system and other organs. Thus, PDE1 enzymes play a critical role in the pathophysiology of diseases through the fundamental regulation of cAMP and cGMP signaling. This comprehensive review provides the current research on PDE1 and its potential utility as a therapeutic target in diseases including the cardiovascular, pulmonary, metabolic, neurocognitive, renal, cancers and possibly others.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107858DOI Listing
April 2021

Progress of clinical translation of handheld and semi-handheld photoacoustic imaging.

Photoacoustics 2021 Jun 19;22:100264. Epub 2021 Mar 19.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.

Photoacoustic imaging (PAI), featuring rich contrast, high spatial/temporal resolution and deep penetration, is one of the fastest-growing biomedical imaging technology over the last decade. To date, numbers of handheld and semi-handheld photoacoustic imaging devices have been reported with corresponding potential clinical applications. Here, we summarize emerged handheld and semi-handheld systems in terms of photoacoustic computed tomography (PACT), optoacoustic mesoscopy (OAMes), and photoacoustic microscopy (PAM). We will discuss each modality in three aspects: laser delivery, scanning protocol, and acoustic detection. Besides new technical developments, we also review the associated clinical studies, and the advantages/disadvantages of these new techniques. In the end, we propose the challenges and perspectives of miniaturized PAI in the future.
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http://dx.doi.org/10.1016/j.pacs.2021.100264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040335PMC
June 2021

Novel mutations in BMP1 result in a patient with autosomal recessive osteogenesis imperfecta.

Mol Genet Genomic Med 2021 Apr 5:e1676. Epub 2021 Apr 5.

Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Osteogenesis imperfecta (OI) is a rare heritable bone disorder that is characterised by increased bone fragility and recurrent fractures. To date, only 19 OI patients have been reported, as caused by BMP1 gene mutations, worldwide. Here, we report a patient with a BMP1 gene mutation to explore the relationship between genotype and phenotype, and the patient was followed up for 4 years.

Methods: Detailed clinical features were collected, and BMP1 mutational analysis was performed by next-generation sequencing and Sanger sequencing.

Results: The patient had recurrent fractures, low bone mass, bone deformities and growth retardation but did not have hearing loss or dentinogenesis imperfecta. Next-generation sequencing and Sanger sequencing revealed a heterozygous novel missense variant (c.362C>T in exon 3, p.Ala121Val) and a heterozygous novel deletion mutation (c.1252delA in exon 10, p.Ser418AlafsX22). The parents of the proband were heterozygous carriers of these mutations. The patient received regular weekly treatment of 70 mg oral alendronate for 3 years, and her BMD Z-score for the femur significantly increased from -1.3 to 0.9 at L1-4 and from -1.7 to -0.1. She had no fracture during 4 years of follow-up.

Conclusion: We discovered two heterozygous novel mutations in an OI patient with BMP1 gene mutations, expanding the spectrum of gene mutations in OI.
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http://dx.doi.org/10.1002/mgg3.1676DOI Listing
April 2021

Mutations Associated with No Durable Clinical Benefit to Immune Checkpoint Blockade in Non-S-Cell Lung Cancer.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300050, China.

(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.
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http://dx.doi.org/10.3390/cancers13061397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003499PMC
March 2021

The Impact of Programmed Death-Ligand 1 Expression on the Prognosis of Early Stage Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Literatures.

Front Oncol 2021 23;11:567978. Epub 2021 Feb 23.

Department of Lung Cancer Surgery, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.

Introduction: Previous studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as biomarker for poor prognosis and survival in advanced-stage non-small cell lung cancer (NSCLC) patients. However, the merit of PD-L1 expression to predict the prognosis of early stage NSCLC patients who underwent complete resection remains controversial. In the present study, we performed a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in patients with early stage resected NSCLC.

Methods: Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched until July 23 2020 for studies evaluating the expression of PD-L1 and the prognosis of resected NSCLCs. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also assessed.

Results: A total of 15 studies involving 3,790 patients were considered in the present meta-analysis. The pooled HR indicated that PD-L1 expression related to a much shorter DFS (HR = 1.56, 95% CI: 1.18-2.05, p < 0.01), as well a significantly worse OS (HR = 1.68, 95% CI: 1.29-2.18, p < 0.01). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male female: OR = 1.27, 95% CI:1.01-1.59, p = 0.038), histology (ADC . SCC: OR = 0.54, 95% CI:0.38-0.77, p = 0.001), TNM stage (I . II-III: OR = 0.45, 95% CI:0.34-0.60, p = 0.000), smoking status (Yes No: OR = 1.43, 95% CI:1.14-1.80, p = 0.002) and lymph node metastasis (N+ N-: OR = 1.97, 95% CI:1.26-3.08, p = 0.003).

Conclusions: The results of this meta-analysis suggest that PD-L1 expression predicts an unfavorable prognosis in early stage resected NSCLCs. The role of personalized anti-PD-L1/PD-1 immunotherapy in the adjuvant settings of resected NSCLC warrants further investigation.
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http://dx.doi.org/10.3389/fonc.2021.567978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940546PMC
February 2021

Control of data variations in intravital microscopy thrombosis models.

J Thromb Haemost 2020 11;18(11):2823-2825

Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.1111/jth.15062DOI Listing
November 2020

Optical resolution photoacoustic computed microscopy.

Opt Lett 2021 Jan;46(2):372-375

Optical resolution photoacoustic microscopy (ORPAM) has demonstrated both high resolution and rich contrast imaging of optical chromophores in biologic tissues. To date, sensitivity remains a major challenge for ORPAM, which limits the capability of resolving biologic microvascular networks. In this study, we propose and evaluate a new ORPAM modality termed as optical resolution photoacoustic computed microscopy (ORPACM), through the combination of a two-dimensional laser-scanning system with a medical ultrasonographic platform. Apart from conventional ORPAMs, we record multiple photoacoustic (PA) signals using a 128-element ultrasonic transducer array for each pulse excitation. Then, we apply a reconstruction algorithm to recover one depth-resolved PA signal referred to as an A-line, which reveals more detailed information compared with conventional single-element transducer-based ORPAMs. In addition, we carried out both in vitro and in vivo experiments as well as quantitative analyses to show the advanced features of ORPACM.
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http://dx.doi.org/10.1364/OL.411861DOI Listing
January 2021

Research Progress of the Application of Hypothermia in the Eye.

Authors:
Lei Xi

Oxid Med Cell Longev 2020 15;2020:3897168. Epub 2020 Dec 15.

Division of Experimental Vitreoretinal Surgery, Centre for Ophthalmology, University of Tübingen, Schleichstrasse 12/1, 72076 Tübingen, Germany.

Hypothermia is widely used in the medical field to protect organs or tissues from damage. Different research fields have different explanations of the protection mechanism of hypothermia. Hypothermia is also widely used in the field of ophthalmology, for example, in the eye bank, the preservation of corneal tissue and the preservation of the eyeball. Low temperature can also be applied to some ophthalmic diseases, such as allergic conjunctivitis, retinal ischemia, and retinal hypoxia. It is used to relieve eye symptoms or reduce tissue damage. Hypothermic techniques have important applications in ophthalmic surgery, such as corneal refractive surgery, vitrectomy surgery, and ciliary body cryotherapy for end-stage glaucoma. Hypothermia can reduce the inflammation of the cornea and protect the retinal tissue. The eyeball is a complex organ, including collagen tissue of the eyeball wall and retinal nerve tissue and retinal blood vessels. The mechanism of low temperature protecting eye tissue is complicated. It is important to understand the mechanism of hypothermia and its applications in ophthalmology. This review introduces the mechanism of hypothermia and its application in the eye banks, eye diseases (allergic conjunctivitis, retinal ischemia, and hypoxia), and eye surgeries (corneal transplant surgery, corneal refractive surgery, and vitrectomy).
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http://dx.doi.org/10.1155/2020/3897168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758138PMC
December 2020

Numerical Simulation of Swirling Impinging Jet Issuing from a Threaded Hole under Inclined Condition.

Entropy (Basel) 2019 Dec 22;22(1). Epub 2019 Dec 22.

State key Laboratory of Mechanical Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

There are some inclined jet holes in the cooling structure of the leading edge region of gas turbine blades. In order to improve the cooling effect of traditional round holes, this paper proposes to replace the round holes with threaded holes, and studies the complex flow and heat transfer performance of the swirling impinging jet (SIJ) issuing from the 45° threaded holes in the inclined condition by numerical simulation. The influencing factors include jet inclination angle (45°-90°), jet-to-plate distance ( = 2, 4, 6), and Reynolds number (6000-24,000). The results show that the inclination angle and jet-to-plate distance have a great influence on the size, shape, and position of vortices in the jet space, while the Reynolds number has little effect on the vortices. In the inclined state, the impinging cooling effect of the swirling impinging jet is better than that of the circular impinging jet (CIJ), both heat transfer coefficients will degrade significantly when the inclination angle is 45°. When the inclination angle is greater than 45°, compared with the round hole, the enhanced heat transfer region for the swirling jet is in the region of r/d < 3, while both of the numbers in the wall jet region are weak, with a value of just 20. At the same time, with the increasing of the inclination angle (α > 45°), the average number on target surface holds a constant value. Under the inclined conditions, the heat transfer coefficient on the target surface for the swirling jet is increased totally with the increasing of the , but when the is larger than 18,000, the rate of enhanced heat transfer gradually weakens.
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http://dx.doi.org/10.3390/e22010015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516431PMC
December 2019

Three-dimensional visualization and analysis of flowing droplets in microchannels using real-time quantitative phase microscopy.

Lab Chip 2021 01;21(1):75-82

School of Mechanical Engineering and Electronic Information, China University of Geosciences, Wuhan, 430074, China.

Recent years have witnessed the development of droplet-based microfluidics as a useful and effective tool for high-throughput analysis in biological, chemical and environmental sciences. Despite the flourishing development of droplet manipulation techniques, only a few methods allow for label-free and quantitative inspection of flowing droplets in microchannels in real-time and in three dimensions (3-D). In this work, we propose and demonstrate the application of a real-time quantitative phase microscopy (RT-QPM) technique for 3-D visualization of droplets, and also for full-field and label-free measurement of analyte concentration distribution in the droplets. The phase imaging system consists of a linear-CCD-based holographic microscopy configuration and an optofluidic phase-shifting element, which can be used for retrieving quantitative phase maps of flowing objects in the microchannels with a temporal resolution only limited to the frame rate of the CCD camera. To demonstrate the capabilities of the proposed imaging technique, we have experimentally validated the 3-D image reconstruction of the droplets generated in squeezing and dripping regimes and quantitatively investigated the volumetric and morphological variation of droplets as well as droplet parameters related to the depth direction under different flow conditions. We also demonstrated the feasibility of using this technique, as a refractive index sensor, for in-line quantitative measurement of carbamide analyte concentration within the flowing droplets.
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http://dx.doi.org/10.1039/d0lc00917bDOI Listing
January 2021

LINC00565 promotes the progression of colorectal cancer by upregulating EZH2.

Oncol Lett 2021 Jan 18;21(1):53. Epub 2020 Nov 18.

Department of Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu 214400, P.R. China.

The present study aimed to illustrate the role of LINC00565 in aggravating colorectal cancer (CRC) by targeting enhancer of zeste homolog 2 (EZH2). The relative levels of LINC00565 and EZH2 in CRC tissues, based on their Tumor-Node-Metastasis stage and tumor size, were detected by reverse transcription-quantitative polymerase chain reaction. The diagnostic value of LINC00565 in CRC was assessed by depicting receiver operating characteristic curves. Pearson's correlation test was applied to analyze the expression correlation between LINC00565 and EZH2 in CRC tissues. The transfection efficacy of three LINC00565 small interfering RNAs was examined in CRC HCT116 and SW480 cell lines. After knockdown of LINC00565, the proliferative and migratory abilities of CRC cells were detected by Cell Counting Kit-8 and Transwell assays, respectively. The subcellular distribution of LINC00565 was analyzed, and the interaction between LINC00565 and EZH2 was determined by RNA immunoprecipitation. Finally, co-regulation of LINC00565 and EZH2 on CRC cell functions was explored by performing rescue experiments. Results showed that LINC00565 was upregulated in CRC tissues, especially in patients with stage III+IV and in those with large tumor sizes, suggesting its diagnostic value in CRC. EZH2 was also upregulated in CRC tissues, showing a positive correlation with LINC00565. LINC00565 was mainly expressed in the cytoplasm and was found to bind with EZH2. Validation was performed by overexpressing EZH2, which abolished the role of silenced LINC00565 in regulating proliferative and migratory abilities in CRC. Therefore, the upregulation of LINC00565 in CRC tissues was found to stimulate the aggravation of CRC by upregulating EZH2.
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http://dx.doi.org/10.3892/ol.2020.12314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709565PMC
January 2021

Sublobar Resection Versus Lobectomy for Early-Stage Pulmonary Carcinoid Tumors ≤3 cm in Size: A SEER Population-Based Study.

Ann Surg 2020 Nov 13. Epub 2020 Nov 13.

Department of Lung Cancer Surgery.

Objective: This study aimed to determine the optimal surgical procedure for early-stage pulmonary carcinoids (PCs).

Background: PCs, comprising typical carcinoids (TCs) and atypical carcinoids (ACs), are rare low-grade malignant tumors. We determine the optimal surgical management for early-stage PCs using data from the Surveillance, Epidemiology, and End Results registry.

Methods: Clinical and survival data of patients with early-stage PC tumors with a diameter ≤3 cm were retrieved. The Kaplan-Meier method and log-rank tests were used to assess the differences in overall survival (OS). Subgroup analyses were also performed. To reduce the inherent bias of retrospective studies, two propensity score matching (PSM) analysis with (PSM2) or without (PSM1) consideration of lymph node assessment were performed.

Results: In total, 2,934 patients with PCs, including 2,741 (93.42%) with TCs and 193 (6.58%) with ACs, were recruited. After PSM1 analysis, TC patients in the lobectomy group had a significantly better OS than those in the sublobar resection group (P = 0.0067), which is more remarkable for patients with a tumor diameter of 2 cm < T ≤ 3 cm (P = 0.0345) and those aged <70 years (P = 0.0032). However, survival benefits were not found after PSM2 analysis which balanced lymph node assessment. In multivariate cox analysis, ag<70y, female, TC histology and adequate lymph node assessment were associated with better OS.

Conclusions: Sublobar resection may not significantly compromise the long-term oncological outcomes in early-stage PCs ≤3 cm in size if lymph node assessment is performed adequately. Further validation in large randomized clinical trials is warranted.
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http://dx.doi.org/10.1097/SLA.0000000000004593DOI Listing
November 2020

Circular RNA Signature in Lung Adenocarcinoma: A MiOncoCirc Database-Based Study and Literature Review.

Front Oncol 2020 9;10:523342. Epub 2020 Oct 9.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a structure of covalently closed continuous loops, which can regulate gene expression by acting as a microRNA sponge or through other mechanisms. Recent studies have identified that the expression of candidate circRNAs are dysregulated in various tumors and hence are considered as promising diagnostic or therapeutic targets across cancer types. However, the expression and function of circRNAs in lung adenocarcinoma (LUAD) remains unclear. In this article, we investigated the expression of circRNAs in LUAD via MiOncoCirc, which is the first and comprehensive database characterizing circRNAs across >2,000 cancer samples using an exome capture RNA sequencing. We identified seven abnormally expressed circRNAs in LUAD, including circCDR1-AS, circHIPK3, circFNDC3B, circPCMTD1, circRHOBTB3, circFAM13B, and circMAN1A2, as well as conducted a literature review about the function and features of these circRNAs. Previous studies have demonstrated that circCDR1-AS, circMAN1A2, and circHIPK3 were upregulated and significantly correlated with a poor survival, or promoted the tumor progression in lung cancer, whereas other circRNAs have not been fully explored. Besides, we reviewed all the publications regarding circRNAs and LUAD, and noticed that the dysregulation of these circRNAs impacts the development of LUAD through a variety of regulatory mechanisms. In conclusion, the underlying mechanisms of aberrant expression and functions of circRNAs in LUAD are worthy of being further investigated.
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http://dx.doi.org/10.3389/fonc.2020.523342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581697PMC
October 2020

Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets.

Acta Pharmacol Sin 2020 Dec 27;41(12):1539-1546. Epub 2020 Oct 27.

Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, 23298-0204, USA.

The pandemic of coronavirus disease 2019 (COVID-19) and its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the greatest current threat to global public health. The highly infectious SARS-CoV-2 virus primarily attacks pulmonary tissues and impairs gas exchange leading to acute respiratory distress syndrome (ARDS) and systemic hypoxia. The current pharmacotherapies for COVID-19 largely rely on supportive and anti-thrombi treatment and the repurposing of antimalarial and antiviral drugs such as hydroxychloroquine and remdesivir. For a better mechanistic understanding of COVID-19, our present review focuses on its primary pathophysiologic features: hypoxia and cytokine storm, which are a prelude to multiple organ failure and lethality. We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS-CoV-2, since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). In addition, the protein targets of HIF-1α are involved with the activation of pro-inflammatory cytokine expression and the subsequent inflammatory process. Furthermore, we hypothesized a potential utility of so-called "hypoxic conditioning" to activate HIF-1α-induced cytoprotective signaling for reduction of illness severity and improvement of vital organ function in patients with COVID-19. Taken together, we would propose further investigations into the hypoxia-related molecular mechanisms, from which novel targeted therapies can be developed for the improved management of COVID-19.
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http://dx.doi.org/10.1038/s41401-020-00554-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588589PMC
December 2020

High expression of squamous cell carcinoma antigen in poorly differentiated adenocarcinoma of the stomach: A case report.

World J Clin Cases 2020 Oct;8(19):4572-4578

Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

Background: Squamous cell carcinoma antigen (SCCA) is regarded as a specific indicator of epithelial malignancies and is widely used in the diagnosis of squamous cell carcinoma (SCC). However, the expression of SCCA in gastric adenocarcinoma has not been studied in detail.

Case Summary: A 52-year-old man was admitted to our hospital for a 2.5 cm × 2.5 cm ulcer at the antrum-body junction with dull pain and fullness in the upper abdomen for 2 mo. His pre-surgery serological testing results showed 0.51 ng/mL SCCA (reference interval, < 1.5 ng/mL) and 9.9 ng/mL carcinoembryonic antigen (reference range, < 4.7 ng/mL). He underwent radical distal gastrectomy and Roux-en Y anastomosis and was diagnosed with poorly differentiated mucinous adenocarcinoma (Lauren classification: Diffuse) by pathological examination of the resected lesion. Immunohistochemistry showed that SCCA was highly expressed in the cytoplasm of cancer cells. After surgery, the patient received an S-1 adjuvant chemotherapy regimen for six cycles containing tegafur, gimeracil, and oteracil potassium. He showed no sign of recurrence or metastasis within 24-mo follow-up.

Conclusion: This is a frontal report of SCCA overexpression in poorly differentiated adenocarcinoma of the stomach.
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http://dx.doi.org/10.12998/wjcc.v8.i19.4572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559675PMC
October 2020

Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta.

J Bone Miner Metab 2021 May 17;39(3):416-422. Epub 2020 Oct 17.

Department of Osteoporosis and Bone Disease, Shanghai Clinical Research Center of Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Introduction: Osteogenesis imperfecta (OI) is a well-known heritable disorder of connective tissue characterized by skeletal fragility and low bone mass. Nearly 90% of patients with OI have disease variants in COL1A1 and COL1A2 that encode for the α1 and α2 chains of type I collagen.

Materials And Methods: A retrospective analysis of 185 probands who were diagnosed with OI in Shanghai Jiao Tong University Affiliated Sixth People's Hospital from March 2005 to December 2019 was performed.

Results: A total of 140 mutations in COL1A1 and 45 mutations in COL1A2 were identified, of which 18 variations were novel. In the phenotype analysis, there were more sporadic cases than familial OI cases in China (54.6% vs. 45.4%, P < 0.001). A total of 98.9% of patients presented with a fracture history. The most common fracture sites were extremity long bones (femur, tibia-fibula and radius-ulna accounted for 36.6%, 17.1% and 11.7%, respectively). Patients with OI types III and IV, especially type III, had a higher proportion of dentinogenesis imperfecta (DI) than patients with OI type I (55% vs. 28%, P < 0.001). Interestingly, G767S and D1219N in COL1A1 and G337S in COL1A2 were the most frequent (3.52%, 2.11% and 8.89%, respectively), which seem to be hotspot mutations in the COL1A1 and COL1A2 genes in Chinese patients.

Conclusions: This study describes the mutations in the main pathogenic genes, COL1A1 and COL1A2, and the clinical characteristics of osteogenesis imperfecta in China. Furthermore, these findings help reveal the genetic basis of Asian OI patients and contribute to genetic counselling.
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http://dx.doi.org/10.1007/s00774-020-01163-5DOI Listing
May 2021

Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction.

Int J Mol Sci 2020 Sep 23;21(19). Epub 2020 Sep 23.

Institute of Sports and Exercise Biology, School of Physical Education, Shaanxi Normal University, Xi'an 710119, China.

Pathological remodeling is the main detrimental complication after myocardial infarction (MI). Overproduction of reactive oxygen species (ROS) in infarcted myocardium may contribute to this process. Adequate exercise training after MI may reduce oxidative stress-induced cardiac tissue damage and remodeling. SET and MYND domain containing 1 (Smyd1) is a muscle-specific histone methyltransferase which is upregulated by resistance training, may strengthen sarcomere assembly and myofiber folding, and may promote skeletal muscles growth and hypertrophy. However, it remains elusive if Smyd1 has similar functions in post-MI cardiac muscle and participates in exercise-induced cardioprotection. Accordingly, we investigated the effects of interval treadmill exercise on cardiac function, ROS generation, Smyd1 expression, and sarcomere assembly of F-actin in normal and infarcted hearts. Adult male rats were randomly divided into five groups ( = 10/group): control (C), exercise alone (EX), sham-operated (S), MI induced by permanent ligation of left anterior descending coronary artery (MI), and MI with interval exercise training (MI + EX). Exercise training significantly improved post-MI cardiac function and sarcomere assembly of F-actin. The cardioprotective effects were associated with increased Smyd1, Trx1, cTnI, and α-actinin expression as well as upregulated ratio of phosphorylated AMP-activated protein kinase (AMPK)/AMPK, whereas Hsp90, MuRF1, brain natriuretic peptide (BNP) expression, ROS generation, and myocardial fibrosis were attenuated. The improved post-MI cardiac function was associated with increased Smyd1 expression. In cultured H9C2 cardiomyoblasts, in vitro treatment with HO (50 µmol/L) or AMP-activated protein kinase (AMPK) agonist (AICAR, 1 mmol/L) or their combination for 4 h simulated the effects of exercise on levels of ROS and Smyd1. In conclusion, we demonstrated a novel role of Smyd1 in association with post-MI exercise-induced cardioprotection. The moderate level of ROS-induced upregulation of Smyd1 may be an important target for modulating post-MI cardiac function and remodeling.
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http://dx.doi.org/10.3390/ijms21197010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582695PMC
September 2020

Photoacoustic endoscopy: A progress review.

J Biophotonics 2020 12 1;13(12):e202000217. Epub 2020 Oct 1.

Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.

Endoscopy has been widely used in biomedical imaging and integrated with various optical and acoustic imaging modalities. Photoacoustic imaging (PAI), one of the fastest growing biomedical imaging modalities, is a noninvasive and nonionizing method that owns rich optical contrast, deep acoustic penetration depth, multiscale and multiparametric imaging capability. Hence, it is preferred to miniaturize the volume of PAI and develop an emerged endoscopic imaging modality referred to as photoacoustic endoscopy (PAE). It has been developed for more than one decade since the first report of PAE. Unfortunately, until now, there is no mature photoacoustic endoscopic technique recognized in clinic due to various technical limitations. To address this concern, recent development of new scanning mechanisms, adoption of novel optical/acoustic devices, utilization of superior computation methods and exploration of multimodality strategies have significantly promoted the progress of PAE toward clinic. In this review, we comprehensively reviewed recent progresses in single- and multimodality PAE with new physics, mechanisms and strategies to achieve practical devices for potential applicable scenarios including esophageal, gastrointestinal, urogenital and intravascular imaging. We ended this review with challenges and prospects for future development of PAE.
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http://dx.doi.org/10.1002/jbio.202000217DOI Listing
December 2020