Publications by authors named "Cheng-Yu Chen"

261 Publications

Diffusion Tensor Imaging of the Spinal Cord.

Magn Reson Imaging Clin N Am 2021 May 23;29(2):195-204. Epub 2021 Mar 23.

Department of Medical Imaging, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 110, Taiwan; Translational Imaging Research Center, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 110, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.

Spinal cord often is regarded as one of the last territories in the central nervous system where diffusion tensor imaging (DTI) can be used to probe white matter architecture. This article reviews current progress in spinal cord DTI, starting with anatomic properties and technical challenges that make spinal cord DTI a difficult task. Several possibilities offered by advanced pulse sequences that might overcome the difficulties are addressed, with associated trade-offs and limitations. Potential clinical assistance also is discussed in various spinal cord pathologies, such as myelopathy due to external compression, spinal cord tumors, acute ischemia, traumatic injury, and so forth.
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http://dx.doi.org/10.1016/j.mric.2021.02.002DOI Listing
May 2021

Bioprosthetic versus mechanical mitral valve replacements in patients with rheumatic heart disease.

J Thorac Cardiovasc Surg 2021 Mar 18. Epub 2021 Mar 18.

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan; Center for Big Data Analytics and Statistics, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan City, Taiwan. Electronic address:

Background: Rheumatic heart disease (RHD) remains a critical problem in developed countries. Few studies have compared the long-term outcomes of bioprosthetic valves and mechanical valves in patients with RHD who have received mitral valve (MV) replacement.

Methods: Patients with RHD who received MV replacement with bioprosthetic or mechanical valves were identified between 2000 and 2013 from Taiwan's National Health Insurance Research Database. The primary late outcomes of interest were all-cause mortality and redo MV surgery. Propensity score matching at a 1:1 ratio was performed.

Results: We identified 3638 patients with RHD who underwent MV replacement. Among those patients, 1075 (29.5%) and 2563 (70.5%) chose a bioprosthetic valve and mechanical valve, respectively. After matching, 788 patients were assigned to each group. No significant difference in the risk of in-hospital mortality was observed between groups (P = .920). Higher risks of all-cause mortality (10-year actuarial estimates: 50.6% vs 45.5%; hazard ratio, 1.19; 95% confidence interval, 1.01-1.41; P = .040) and MV reoperation (10-year actuarial estimates: 8.9% vs 0.93%; subdistribution hazard ratio, 4.56; 95% confidence interval, 1.71-12.17; P <.01) were observed in the bioprosthetic valve group. Furthermore, the relative mortality benefit associated with mechanical valves was more apparent in younger patients and the beneficial effect persisted until approximately 65 years of age.

Conclusions: In the patients with RHD who underwent MV replacement, mechanical valves were associated with more favorable long-term outcomes in patients younger than the age of 65 years.
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http://dx.doi.org/10.1016/j.jtcvs.2021.03.033DOI Listing
March 2021

Evaluation of the Swallow-Tail Sign and Correlations of Neuromelanin Signal with Susceptibility and Relaxations.

Tomography 2021 Mar 27;7(2):107-119. Epub 2021 Mar 27.

School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.

The presence of a swallow-tail sign in the nigrosome-1 with hyperintense signal shown on the susceptibility-weighted imaging (SWI) has been shown to be sensitive in detecting the abnormal iron deposits in this area. A systematic evaluation in healthy subjects is required before this tool can be recommended in a widespread application. We evaluated a simple and practical SWI approach using a multiecho gradient-echo sequence with an improved contrast-to-noise ratio (CNR). We also evaluated the association of the neuromelanin imaging contrast behavior with the susceptibility and relaxation measurements. Twenty-five older and 23 young healthy adults were evaluated. The CNRs of the nigrosome-1 were compared along with method and group. Correlations of the nigrosome-1 neuromelanin signal in the neuromelanin-sensitive imaging with CNRs in the susceptibility, T1 and T2 mappings were examined. Two different coils were used to confirm the reproducibility. Compared with the single-echo, multiecho SWI can improve the CNR of the swallow-tail sign. We found significant correlations between neuromelanin signal and CNRs in the susceptibility and T2 mappings, and T1 value. The older subjects exhibited increased CNRs compared with the young adults. No significant difference was observed in the measurements between 20 and 64 channels. The multiecho technique allows the high-quality nigrosome-1 images in SWI and allows for a joint analysis of T2* and quantitative-susceptibility mapping at high spatial resolution. The correlations of neuromelanin-sensitive imaging with susceptibility and T2 imply that the iron content in the nigrosome-1 may have significant influences on the hyperintensity of neuromelanin in the magnetization transfer-related contrast.
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http://dx.doi.org/10.3390/tomography7020010DOI Listing
March 2021

Using the health belief model to explore nursing students' relationships between COVID-19 knowledge, health beliefs, cues to action, self-efficacy, and behavioral intention: A cross-sectional survey study.

Medicine (Baltimore) 2021 Mar;100(11):e25210

Department of Nursing, Registered Nurse, Mennonite Christian Hospital, Taiwan ROC.

Abstract: Nursing educators should equip nursing students with sufficient knowledge about coronavirus disease 2019 (COVID-19), perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, self-efficacy, and behavioral intention in order to prevent the spread of COVID-19.The purpose of this study was to use the health belief model to elucidate nursing students' relationships between knowledge about COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, self-efficacy, and behavioral intention.A cross-sectional survey design was adopted and purposive sampling was utilized. A total of 361 nursing students participated in the study. Quantitative analysis was employed for all data analysis.The findings showed that the nursing students had the following mean scores on knowledge of COVID-19 9.43 [standard deviation (SD)1.19], perceived susceptibility 19.41 (SD2.68), perceived severity 20.31 (SD 4.09), perceived benefits 26.52 (SD 4.08), perceived barriers 15.17 (SD5.88), cues to action 3.30 (SD1.70), self-efficacy 17.68 (SD2.83), and behavioral intention 18.46 (SD2.33). Nursing students' demographic background, knowledge of COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy explained 58.1% of the variance in behavioral intention (R2 = 0.581, F = 29.775, P < .001).Nursing educators can increase nursing students' knowledge of COVID-19, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, cues to action, and self-efficacy as effective means of health promotion to improve their behavioral intention to prevent the spread of COVID-19.
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http://dx.doi.org/10.1097/MD.0000000000025210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982209PMC
March 2021

An annotation-free whole-slide training approach to pathological classification of lung cancer types using deep learning.

Nat Commun 2021 02 19;12(1):1193. Epub 2021 Feb 19.

Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Deep learning for digital pathology is hindered by the extremely high spatial resolution of whole-slide images (WSIs). Most studies have employed patch-based methods, which often require detailed annotation of image patches. This typically involves laborious free-hand contouring on WSIs. To alleviate the burden of such contouring and obtain benefits from scaling up training with numerous WSIs, we develop a method for training neural networks on entire WSIs using only slide-level diagnoses. Our method leverages the unified memory mechanism to overcome the memory constraint of compute accelerators. Experiments conducted on a data set of 9662 lung cancer WSIs reveal that the proposed method achieves areas under the receiver operating characteristic curve of 0.9594 and 0.9414 for adenocarcinoma and squamous cell carcinoma classification on the testing set, respectively. Furthermore, the method demonstrates higher classification performance than multiple-instance learning as well as strong localization results for small lesions through class activation mapping.
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http://dx.doi.org/10.1038/s41467-021-21467-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896045PMC
February 2021

The synergistic effects of quercetin-containing 3D-printed mesoporous calcium silicate/calcium sulfate/poly-ε-caprolactone scaffolds for the promotion of osteogenesis in mesenchymal stem cells.

J Formos Med Assoc 2021 Feb 13. Epub 2021 Feb 13.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Background/purpose: Several growth factors were proven to be effective in the treatment of bone defects and fractures and thus have great potential for bone regeneration applications. However, it needs low-temperature storage and transportation. This study aimed to investigate the herbal extract quercetin, a candidate for natural flavonoid compounds that have been reported to be involved in regulating inflammation and improving immunity and health.

Methods: In this study, we prepared quercetin (Q)/mesoporous calcium silicate calcium sulfate (MSCS)/polycaprolactone (PCL) composite scaffolds using the 3D printing technique, where we immersed it in simulated body fluid (SBF) solution and soaked it for up to 60 days. The characteristics of quercetin scaffold were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), immunofluorescence, and Alizarin Red S staining.

Results: We found precipitation of apatite on the surface of the scaffold. The in vitro results for cell proliferation, cytotoxicity, and immunofluorescence staining revealed that Wharton's jelly mesenchymal stem cells (WJMSCs) with a 2% quercetin (Q2) scaffold were significantly higher in number than with 1% quercetin (Q1) and MSCS scaffolds. The phalloidin staining of cell skeletons on the surface of Q2 revealed powerful cell-to-cell adhesion and high expression of green fluorescence. The Q2 scaffold also had the highest calcium deposit levels based on Alizarin Red S staining in all scaffolds. This indicated that quercetin was able to induce cell growth and mitosis, echoing the previous preliminary results.

Conclusion: Our initial results indicate that this natural herbal extract can be a good bone-based gene substitution for bone regeneration.
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http://dx.doi.org/10.1016/j.jfma.2021.01.024DOI Listing
February 2021

Removal of cadmium from wastewater by magnetic zeolite synthesized from natural, low-grade molybdenum.

Sci Total Environ 2021 Jun 23;772:145355. Epub 2021 Jan 23.

College of Natural Resources and Environment, Joint Institute for Environment & Education, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Zeolite has a high adsorption capacity for heavy metals, but it is difficult to separate from the medium because of its small particle size. In this study, magnetic zeolite was synthesized from natural, low-grade molybdenum ore by adding nano ferroferric oxide (saturation magnetization 83.43 emu/g) directly in the hydrothermal synthesis process, which was used to adsorb cadmium from wastewater. The results of scanning electron microscopy showed that the nano ferroferric oxide was adhered to the surface of the zeolite to make it magnetic. The vibrating sample magnetometer showed that the larger the amount of nano ferroferric oxide added, the higher the saturation magnetization of the magnetic zeolite. The saturation magnetization of the magnetic zeolite with a loading proportion of 25% was 18.18 emu/g with a specific surface area of 459.8 m/g. The adsorption experiments showed that when the pH value is greater than 4, the adsorption capacity of magnetic zeolite is high and stable, and the theoretical maximum adsorption capacity is 204.2 mg Cd/g. Na and Ca have different inhibitory functions on the adsorption capacity. The mapping graphs showed that cadmium is captured by the magnetic zeolite after contact with cadmium, and XRD confirmed the presence of cadmium oxide in the magnetic zeolite after adsorption, XPS and EDS results indicated that ion exchange is one of the main mechanisms of cadmium adsorption by magnetic zeolites, and electrostatic adsorption may also have a contribution.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145355DOI Listing
June 2021

Incorporation of Calcium Sulfate Dihydrate into a Mesoporous Calcium Silicate/Poly-ε-Caprolactone Scaffold to Regulate the Release of Bone Morphogenetic Protein-2 and Accelerate Bone Regeneration.

Biomedicines 2021 Jan 29;9(2). Epub 2021 Jan 29.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei 106319, Taiwan.

Tissue engineering and scaffolds play an important role in tissue regeneration by supporting cell adhesion, proliferation, and differentiation. The design of a scaffold is critical in determining its feasibility, and it is critical to note that each tissue is unique in terms of its morphology and composition. However, calcium-silicate-based scaffolds are undegradable, which severely limits their application in bone regeneration. In this study, we developed a biodegradable mesoporous calcium silicate (MS)/calcium sulfate (CS)/poly-ε-caprolactone (PCL) composite and fabricated a composite scaffold with 3D printing technologies. In addition, we were able to load bone morphogenetic protein-2 (BMP-2) into MS powder via a one-step immersion procedure. The results demonstrated that the MS/CS scaffold gradually degraded within 3 months. More importantly, the scaffold exhibited a gradual release of BMP-2 throughout the test period. The adhesion and proliferation of human dental pulp stem cells on the MS/CS/BMP-2 (MS/CS/B) scaffold were significantly greater than that on the MS/CS scaffold. It was also found that cells cultured on the MS/CS/B scaffold had significantly higher levels of alkaline phosphatase activity and angiogenic-related protein expression. The MS/CS/B scaffold promoted the growth of new blood vessels and bone regeneration within 4 weeks of implantation in rabbits with induced critical-sized femoral defects. Therefore, it is hypothesized that the 3D-printed MS/CS/B scaffold can act both as a conventional BMP-2 delivery system and as an ideal osteoinductive biomaterial for bone regeneration.
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http://dx.doi.org/10.3390/biomedicines9020128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911692PMC
January 2021

Mechanical Thrombectomy and Stenting for Radiation-Induced Carotid Stenosis-Related Stroke: A Case Report.

Case Rep Neurol 2020 Sep-Dec;12(Suppl 1):70-75. Epub 2020 Dec 14.

Department of Neurology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan.

Radiation-induced stenosis of the carotid artery is a significant risk factor for large-vessel ischemic stroke, which usually leads to significant impairment of neurological function. We performed intra-arterial thrombectomy on a 63-year-old male patient who had laryngeal cancer and postradiation carotid stenosis. He presented with acute-onset dysarthria and left hemiplegia. Brain computed tomography perfusion scan showed right middle cerebral artery ischemic change. Angiography confirmed total occlusion of the right internal carotid artery. Intra-arterial mechanical thrombectomy with carotid stenting was performed immediately, and recanalization was achieved. The patient fully recovered and was discharged after a 1-week hospitalization. Our experience suggests that early intervention for radiation-related carotid stenosis might be essential and beneficial for the outcome of large-vessel ischemic stroke.
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http://dx.doi.org/10.1159/000507432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802459PMC
December 2020

Development and biochemical characterization of the monoclonal antibodies for specific detection of the emerging H5N8 and H5Nx avian influenza virus hemagglutinins.

Appl Microbiol Biotechnol 2021 Jan 27;105(1):235-245. Epub 2020 Nov 27.

Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, 106, Taiwan.

The highly pathogenic avian influenza (HPAI) H5N8 virus has been detected in wild birds and poultry worldwide. The threat caused by HPAI H5N8 virus still exists with concerns for human infection. The preparedness for epidemic prevention and decreasing the agricultural and economic lost is extremely important. Hemagglutinin (HA), a surface glycoprotein of influenza viruses, is considered as the major target for detection of the influenza virus subtype in the infected samples. In this study, the recombinant H5N8 HA1 and HA2 proteins were expressed in Escherichia coli, and were utilized to generate two monoclonal antibodies, named 7H6C and YC8. 7H6C can bind the HA proteins of H5N1 and H5N8, but cannot bind the HA proteins of H1N1, H3N2, and H7N9, indicating that it has H5-subtype specificity. In contrast, YC8 can bind the HA proteins of H1N1, H5N1, and H5N8, but cannot bind the HA proteins of H3N2 and H7N9, indicating that it has H1-subtype and H5-subtype specificity. The epitope sequences recognized by 7H6C are located in the head domain of H5N8 HA, and are highly conserved in H5 subtypes. The epitope sequences recognized by YC8 are located in the stalk domain of H5N8 HA, and are highly conserved among the H1 and H5 subtypes. 7H6C and YC8 can be applied for specific detection of the HA proteins of H5N8 and H5Nx avian influenza viruses. KEY POINTS: • The mAb 7H6C or YC8 was generated by using the HA1 or HA2 of the HPAI H5N8 virus as the immunogen. • 7H6C recognized the head domain of H5N8 HA, and YC8 recognized the stalk domain of H5N8 HA. • 7H6C and YC8 can detect the HA proteins of H5Nx subtypes specifically.
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http://dx.doi.org/10.1007/s00253-020-11035-7DOI Listing
January 2021

Pharmaceutical Evaluation of Honokiol and Magnolol on Apoptosis and Migration Inhibition in Human Bladder Cancer Cells.

Front Pharmacol 2020 6;11:549338. Epub 2020 Nov 6.

Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Among herbal medicines, magnolia bark extract, particularly its components honokiol (Hono) and magnolol (Mag), has been widely documented to have antineoplastic properties. The present study aimed to evaluate the synergism of Hono and Mag in bladder cancer therapy both and . Treatment with Mag alone at concentrations up to 80 μM failed to have an antiproliferative effect. In contrast, the combination of Hono and Mag at 40 μM decreased viability, caused cell cycle arrest and enhanced the proportion of Annexin V/7AAD-positive cells. Moreover, Mag with Hono at 40 μM induced caspase 3-dependent apoptosis and autophagy. Neither Hono nor Mag alone had an anti-migratory effect on bladder cancer cells. In contrast, Hono and Mag at 20 μM inhibited the motility of TSGH8301 and T24 cells in wound-healing and Transwell assays. The above phenomena were further confirmed by decreased phosphorylated focal adhesion kinase (p-FAK), p-paxillin, integrin β1, and integrin β3 protein levels. In a nude mouse xenograft model, Mag/Hono administration preferentially retarded T24 tumor progression, which was consistent with the results of cellular experiments. Current findings suggest Hono and Mag treatment as a potential anticancer therapy for both low- and high-grade urothelial carcinoma.
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http://dx.doi.org/10.3389/fphar.2020.549338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677562PMC
November 2020

Solution structures of the Shewanella woodyi H-NOX protein in the presence and absence of soluble guanylyl cyclase stimulator IWP-051.

Protein Sci 2021 Feb 10;30(2):448-463. Epub 2020 Dec 10.

Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, USA.

Heme-nitric oxide/oxygen binding (H-NOX) domains bind gaseous ligands for signal transduction in organisms spanning prokaryotic and eukaryotic kingdoms. In the bioluminescent marine bacterium Shewanella woodyi (Sw), H-NOX proteins regulate quorum sensing and biofilm formation. In higher animals, soluble guanylyl cyclase (sGC) binds nitric oxide with an H-NOX domain to induce cyclase activity and regulate vascular tone, wound healing and memory formation. sGC also binds stimulator compounds targeting cardiovascular disease. The molecular details of stimulator binding to sGC remain obscure but involve a binding pocket near an interface between H-NOX and coiled-coil domains. Here, we report the full NMR structure for CO-ligated Sw H-NOX in the presence and absence of stimulator compound IWP-051, and its backbone dynamics. Nonplanar heme geometry was retained using a semi-empirical quantum potential energy approach. Although IWP-051 binding is weak, a single binding conformation was found at the interface of the two H-NOX subdomains, near but not overlapping with sites identified in sGC. Binding leads to rotation of the subdomains and closure of the binding pocket. Backbone dynamics are similar across both domains except for two helix-connecting loops, which display increased dynamics that are further enhanced by compound binding. Structure-based sequence analyses indicate high sequence diversity in the binding pocket, but the pocket itself appears conserved among H-NOX proteins. The largest dynamical loop lies at the interface between Sw H-NOX and its binding partner as well as in the interface with the coiled coil in sGC, suggesting a critical role for the loop in signal transduction.
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http://dx.doi.org/10.1002/pro.4005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784750PMC
February 2021

A network-based approach to deciphering a dynamic microbiome's response to a subtle perturbation.

Sci Rep 2020 11 11;10(1):19530. Epub 2020 Nov 11.

Bioenergy Research Center, National Taiwan University, Taipei, Taiwan.

Over the past decades, one main issue that has emerged in ecological and environmental research is how losses in biodiversity influence ecosystem dynamics and functioning, and consequently human society. Although biodiversity is a common indicator of ecosystem functioning, it is difficult to measure biodiversity in microbial communities exposed to subtle or chronic environmental perturbations. Consequently, there is a need for alternative bioindicators to detect, measure, and monitor gradual changes in microbial communities against these slight, chronic, and continuous perturbations. In this study, microbial networks before and after subtle perturbations by adding S. acidaminiphila showed diverse topological niches and 4-node motifs in which microbes with co-occurrence patterns played the central roles in regulating and adjusting the intertwined relationships among microorganisms in response to the subtle environmental changes. This study demonstrates that microbial networks are a good bioindicator for chronic perturbation and should be applied in a variety of ecological investigations.
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http://dx.doi.org/10.1038/s41598-020-73920-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659003PMC
November 2020

Radiomic Immunophenotyping of GSEA-Assessed Immunophenotypes of Glioblastoma and Its Implications for Prognosis: A Feasibility Study.

Cancers (Basel) 2020 Oct 19;12(10). Epub 2020 Oct 19.

Translational Imaging Research Center, Taipei Medical University Hospital, Taipei 110, Taiwan.

Characterization of immunophenotypes in glioblastoma (GBM) is important for therapeutic stratification and helps predict treatment response and prognosis. Radiomics can be used to predict molecular subtypes and gene expression levels. However, whether radiomics aids immunophenotyping prediction is still unknown. In this study, to classify immunophenotypes in patients with GBM, we developed machine learning-based magnetic resonance (MR) radiomic models to evaluate the enrichment levels of four immune subsets: Cytotoxic T lymphocytes (CTLs), activated dendritic cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs). Independent testing data and the leave-one-out cross-validation method were used to evaluate model effectiveness and model performance, respectively. We identified five immunophenotypes (G1 to G5) based on the enrichment level for the four immune subsets. G2 had the worst prognosis and comprised highly enriched MDSCs and lowly enriched CTLs. G3 had the best prognosis and comprised lowly enriched MDSCs and Tregs and highly enriched CTLs. The average accuracy of T1-weighted contrasted MR radiomics models of the enrichment level for the four immune subsets reached 79% and predicted G2, G3, and the "immune-cold" phenotype (G1) according to our radiomics models. Our radiomic immunophenotyping models feasibly characterize the immunophenotypes of GBM and can predict patient prognosis.
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http://dx.doi.org/10.3390/cancers12103039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603270PMC
October 2020

Decreased stroke risk with combined traditional Chinese and western medicine in patients with ischemic heart disease: A real-world evidence.

Medicine (Baltimore) 2020 Oct;99(42):e22654

Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine.

Both ischemic heart disease (IHD) and stroke are major causes of death worldwide. We investigated the effects of combined Traditional Chinese medicine (TCM) and western medicine (WM) on stroke risk in IHD patients.Taiwanese patients with IHD were enrolled in the TCM study during their outpatient visit. Stroke events after TCM or non-TCM treatment were examined. Chi-square tests and Student t-tests were used to examine differences between patients using and not using TCM. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs). Sex, age, and comorbidities were included in a multivariable Cox model to estimate the adjusted HR (aHR). The survival probability and the probability free of stroke were calculated by the Kaplan-Meier method.There were 733 IHD patients using TCM and 733 using non-TCM treatment, with the same proportion of sex and age within each cohort. Using single Chinese herb such as Dan Shen, San Qi, or Chuan Xiong would have lower stroke events and lower aHR than non-TCM in IHD patients. There was 0.3-fold lower stroke risk in IHD patients with combination TCM and non-TCM treatment (95% CI = 0.11-0.84, P = .02). Moreover, the survival rate was higher (P < .001) and the incidence of hemorrhagic stroke was significantly lower (P = .04) in IHD patients with TCM treatment.IHD patients using combined TCM and WM had a higher survival rate and lower risk of new onset stroke, especially hemorrhagic stroke than those who did not use TCM treatment.
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http://dx.doi.org/10.1097/MD.0000000000022654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571976PMC
October 2020

Mitral valve repair versus replacement in patients with rheumatic heart disease.

J Thorac Cardiovasc Surg 2020 Aug 29. Epub 2020 Aug 29.

Department of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taiwan.

Background: Rheumatic heart disease remains a major cause of cardiovascular death worldwide. Limited real-world nationwide data are available to compare the long-term outcomes between mitral valve repair and replacement in rheumatic heart disease.

Methods: We identified adult patients with rheumatic heart disease who underwent mitral valve repair or replacement surgery between 2000 and 2013 from Taiwan's National Health Insurance Research Database. Outcomes of interest included operation-related complications, all-cause mortality, and mitral valve reoperation rate. Propensity score matching at a 1:1 ratio was conducted to mitigate possible confounding factors.

Results: A total of 5086 patients with rheumatic heart disease who underwent mitral valve surgery were identified. Of those, 489 (9.6%) and 4597 (90.4%) underwent mitral valve repair and mitral valve replacement, respectively. After propensity score matching was applied, each group had 467 patients. No difference in risk of in-hospital mortality was observed between groups. With a mean follow-up of 6 years, the mitral valve repair group had comparable risks of all-cause mortality with the mitral valve replacement group (33.4% vs 32.5%; hazard ratio, 1.01; 95% confidence interval, 0.81-1.25). However, higher risks of mitral valve reoperation were observed in the mitral valve repair group (subdistribution hazard ratio, 4.32; 95% confidence interval, 2.02-9.23). Previous percutaneous transvenous mitral commissurotomy was identified as a risk factor of mitral valve reoperation in the repair group.

Conclusions: Among patients with rheumatic heart disease, mitral valve repair is not associated with superior long-term outcomes. Patients should be carefully selected for mitral valve repair because of its higher reoperation rate, particularly those with previous percutaneous transvenous mitral commissurotomy.
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http://dx.doi.org/10.1016/j.jtcvs.2020.07.117DOI Listing
August 2020

XGBoost Improves Classification of MGMT Promoter Methylation Status in IDH1 Wildtype Glioblastoma.

J Pers Med 2020 Sep 15;10(3). Epub 2020 Sep 15.

Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei City 106, Taiwan.

Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM.
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http://dx.doi.org/10.3390/jpm10030128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563334PMC
September 2020

Maternal gut microbes shape the early-life assembly of gut microbiota in passerine chicks via nests.

Microbiome 2020 09 11;8(1):129. Epub 2020 Sep 11.

Biodiversity Research Center, Academia Sinica, Taipei, 115201, Taiwan.

Background: Knowledge is growing on how gut microbiota are established, but the effects of maternal symbiotic microbes throughout early microbial successions in birds remain elusive. In this study, we examined the contributions and transmission modes of maternal microbes into the neonatal microbiota of a passerine, the zebra finch (Taeniopygia guttata), based on fostering experiments.

Results: Using 16S rRNA amplicon sequencing, we found that zebra finch chicks raised by their biological or foster parents (the society finch Lonchura striata domestica) had gut microbial communities converging with those of the parents that reared them. Moreover, source-tracking models revealed high contribution of zebra finches' oral cavity/crop microbiota to their chicks' early gut microbiota, which were largely replaced by the parental gut microbiota at later stages. The results suggest that oral feeding only affects the early stage of hatchling gut microbial development.

Conclusions: Our study indicates that passerine chicks mainly acquire symbionts through indirect maternal transmission-passive environmental uptake from nests that were smeared with the intestinal and cloacal microbes of parents that raised them. Gut microbial diversity was low in hand-reared chicks, emphasizing the importance of parental care in shaping the gut microbiota. In addition, several probiotics were found in chicks fostered by society finches, which are excellent foster parents for other finches in bird farms and hosts of brood parasitism by zebra finches in aviaries; this finding implies that avian species that can transfer probiotics to chicks may become selectively preferred hosts of brood parasitism in nature. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00896-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488855PMC
September 2020

PSMB8 inhibition decreases tumor angiogenesis in glioblastoma through vascular endothelial growth factor A reduction.

Cancer Sci 2020 Nov 8;111(11):4142-4153. Epub 2020 Sep 8.

Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.

Glioblastoma, also known as glioblastoma multiforme (GBM), is a fast-growing tumor and the most aggressive brain malignancy. Proteasome subunit beta type-8 (PSMB8) is one of the 17 essential subunits for the complete assembly of the 20S proteasome complex. The aim of the present study was to evaluate the role of PSMB8 expression in GBM progression and angiogenesis. PSMB8 expression in glioblastoma LN229 and U87MG was knocked down by siRNA or inducible shRNA both in vitro and in vivo. After PSMB8 reduction, cell survival, migration, invasion, angiogenesis, and the related signaling cascades were evaluated. An orthotopic mouse tumor model was also provided to examine the angiogenesis within tumors. A GEO profile analysis indicated that high expression of PSMB8 mRNA in GBM patients was correlated with a low survival rate. In immunohistochemistry analysis, PSMB8 expression was higher in high-grade than in low-grade brain tumors. The proliferation, migration, and angiogenesis of human GBM cells were decreased by PSMB8 knockdown in vitro. Furthermore, phosphorylated focal adhesion kinase (p-FAK), p-paxillin, MMP2, MMP9, and cathepsin B were significantly reduced in LN229 cells. Integrin β1 and β3 were reduced in HUVEC after incubation with LN229-conditioned medium. In an orthotopic mouse tumor model, inducible knockdown of PSMB8 reduced the expression of vascular endothelial growth factor (VEGF), VEGF receptor, and CD31 as well as the progression of human glioblastoma. In this article, we demonstrated the role of PSMB8 in glioblastoma progression, especially neovascularization in vitro and in vivo. These results may provide a target for the anti-angiogenic effect of PSMB8 in glioblastoma therapy in the future.
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http://dx.doi.org/10.1111/cas.14625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648028PMC
November 2020

Effects of Trace Irrigation at Different Depths on Transcriptome Expression Pattern in Cotton ( L.) Leaves.

Biomed Res Int 2020 27;2020:7248513. Epub 2020 Jul 27.

Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China.

Drought is a limiting factor for cotton productivity and quality. Irrigation could increase cotton yield. This study is aimed at formulating a proper irrigation depth for cotton at China' Inner Mongolia and at investigating the molecular mechanism underlying the difference induced by irrigation. Transcriptomic analysis was carried out to reveal the global transcriptome profiles on the leaves of cotton seedlings ( L. cv. "Zhongmian 92") with trace irrigation tapes at 30 cm (D30) and 50 cm (D50) underground. The differentially expressed genes (DEGs) were identified and clustered by functional enrichment analysis. The results showed that no significant differences were found in the lint percentage. The yields of unpinned and lint cotton were increased by the D30 regime but decreased by the D50 regime. Transcriptomic analysis showed that 4,549 nonoverlapped DEGs were identified by comparative analysis. Transcription factors, including , , , and , were altered between D50 and D30. The D50 regime induced more DEGs compared with the D30 regime, which was associated with plant tolerance to abiotic stresses and drought. In conclusion, trace irrigation at 30 cm underground was suitable for cotton irrigation at China's Inner Mongolia, while the D50 irrigation regime influenced the cotton yield via drought stress in cotton plants.
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http://dx.doi.org/10.1155/2020/7248513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403946PMC
April 2021

Chinese herbal medicine SS-1 inhibits T cell activation and abrogates T responses in Sjögren's syndrome.

J Formos Med Assoc 2021 Jan 30;120(1 Pt 3):651-659. Epub 2020 Jul 30.

Graduate Institute of Integrated Medicine, and Graduate Institute of Acupuncture Science, College of Chinese Medicine, and Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan. Electronic address:

Background/purpose: Sjögren's syndrome (SS) is an autoimmune disease and its conventional treatment has exhibited limited therapeutic efficacy. Traditional Chinese medicine has been demonstrated to ameliorate the sicca symptoms of SS by decreasing the level of T1 and T2 cytokines and increasing salivary flow rate. A newly designed traditional Chinese medicine, SS-1, showed improved efficacy in alleviating the dryness symptoms of SS patients in the National Taiwan SS cohort investigation. Here, we investigated the effect of SS-1 on T cell responses.

Methods: SS-1 was authenticated and its major compounds were verified by high-performance liquid chromatography. We examined the effects of SS-1 on the activation and T1, T2, and T17 polarization of murine T cells. We also determined the level of T1, T2, and T17 cytokine RNA in peripheral blood mononuclear cells of SS patients before and after SS-1 treatment.

Results: SS-1 treatment inhibits the activation and T1, T2, and IL-17AIFNγ T polarization of murine T cells. SS-1 treatment also significantly reduces IFN-γ, IL-4, and IL-13 expression, and moderately reduces IL-17A expression in peripheral blood mononuclear cells of SS patients.

Conclusion: Our results suggest that SS-1 inhibits T cell activation and diminishes T1, T2, and IL-17IFN-γ T responses in SS patients.
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http://dx.doi.org/10.1016/j.jfma.2020.07.024DOI Listing
January 2021

Machine learning-based segmentation of ischemic penumbra by using diffusion tensor metrics in a rat model.

J Biomed Sci 2020 Jul 15;27(1):80. Epub 2020 Jul 15.

Department of Medical Imaging, Taipei Medical University Hospital, No.250, Wu-Hsing St, Taipei, 11031, Taiwan.

Background: Recent trials have shown promise in intra-arterial thrombectomy after the first 6-24 h of stroke onset. Quick and precise identification of the salvageable tissue is essential for successful stroke management. In this study, we examined the feasibility of machine learning (ML) approaches for differentiating the ischemic penumbra (IP) from the infarct core (IC) by using diffusion tensor imaging (DTI)-derived metrics.

Methods: Fourteen male rats subjected to permanent middle cerebral artery occlusion (pMCAO) were included in this study. Using a 7 T magnetic resonance imaging, DTI metrics such as fractional anisotropy, pure anisotropy, diffusion magnitude, mean diffusivity (MD), axial diffusivity, and radial diffusivity were derived. The MD and relative cerebral blood flow maps were coregistered to define the IP and IC at 0.5 h after pMCAO. A 2-level classifier was proposed based on DTI-derived metrics to classify stroke hemispheres into the IP, IC, and normal tissue (NT). The classification performance was evaluated using leave-one-out cross validation.

Results: The IC and non-IC can be accurately segmented by the proposed 2-level classifier with an area under the receiver operating characteristic curve (AUC) between 0.99 and 1.00, and with accuracies between 96.3 and 96.7%. For the training dataset, the non-IC can be further classified into the IP and NT with an AUC between 0.96 and 0.98, and with accuracies between 95.0 and 95.9%. For the testing dataset, the classification accuracy for IC and non-IC was 96.0 ± 2.3% whereas for IP and NT, it was 80.1 ± 8.0%. Overall, we achieved the accuracy of 88.1 ± 6.7% for classifying three tissue subtypes (IP, IC, and NT) in the stroke hemisphere and the estimated lesion volumes were not significantly different from those of the ground truth (p = .56, .94, and .78, respectively).

Conclusions: Our method achieved comparable results to the conventional approach using perfusion-diffusion mismatch. We suggest that a single DTI sequence along with ML algorithms is capable of dichotomizing ischemic tissue into the IC and IP.
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http://dx.doi.org/10.1186/s12929-020-00672-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362663PMC
July 2020

Assessment of the Release of Vascular Endothelial Growth Factor from 3D-Printed Poly-ε-Caprolactone/Hydroxyapatite/Calcium Sulfate Scaffold with Enhanced Osteogenic Capacity.

Polymers (Basel) 2020 Jun 29;12(7). Epub 2020 Jun 29.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei 10617, Taiwan.

Vascular endothelial growth factor (VEGF) is one of the most crucial growth factors and an assistant for the adjustment of bone regeneration. In this study, a 3D scaffold is fabricated using the method of fused deposition modeling. Such a fabricated method allows us to fabricate scaffolds with consistent pore sizes, which could promote cellular ingrowth into scaffolds. Therefore, we drafted a plan to accelerate bone regeneration via VEGF released from the hydroxyapatite/calcium sulfate (HACS) scaffold. Herein, HACS will gradually degrade and provide a suitable environment for cell growth and differentiation. In addition, HACS scaffolds have higher mechanical properties and drug release compared with HA scaffolds. The drug release profile of the VEGF-loaded scaffolds showed that VEGF could be loaded and released in a stable manner. Furthermore, initial results showed that VEGF-loaded scaffolds could significantly enhance the proliferation of human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVEC). In addition, angiogenic- and osteogenic-related proteins were substantially increased in the HACS/VEGF group. Moreover, in vivo results revealed that HACS/VEGF improved the regeneration of the rabbit's femur bone defect, and VEGF loading improved bone tissue regeneration and remineralization after implantation for 8 weeks. All these results strongly imply that the strategy of VEGF loading onto scaffolds could be a potential candidate for future bone tissue engineering.
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http://dx.doi.org/10.3390/polym12071455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408109PMC
June 2020

Controlling photoionization using attosecond time-slit interferences.

Proc Natl Acad Sci U S A 2020 May 30;117(20):10727-10732. Epub 2020 Apr 30.

Department of Physics, Lund University, 22100 Lund, Sweden

When small quantum systems, atoms or molecules, absorb a high-energy photon, electrons are emitted with a well-defined energy and a highly symmetric angular distribution, ruled by energy quantization and parity conservation. These rules are based on approximations and symmetries which may break down when atoms are exposed to ultrashort and intense optical pulses. This raises the question of their universality for the simplest case of the photoelectric effect. Here we investigate photoionization of helium by a sequence of attosecond pulses in the presence of a weak infrared laser field. We continuously control the energy of the photoelectrons and introduce an asymmetry in their emission direction, at variance with the idealized rules mentioned above. This control, made possible by the extreme temporal confinement of the light-matter interaction, opens a road in attosecond science, namely, the manipulation of ultrafast processes with a tailored sequence of attosecond pulses.
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http://dx.doi.org/10.1073/pnas.1921138117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245115PMC
May 2020

Corrigendum to Immuohistochemical score of matrix metalloproteinase-1 may indicate the severity of symptomatic cervical and lumbar disc degeneration' [The Spine Journal 20 (2020) 124-137].

Spine J 2020 Jul 25;20(7):1163. Epub 2020 Apr 25.

School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.. Electronic address:

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http://dx.doi.org/10.1016/j.spinee.2020.02.013DOI Listing
July 2020

Efficacy and Safety of Wendan Decoction for Acute Brain Injury: A Randomized Controlled Study.

J Altern Complement Med 2020 May 24;26(5):392-397. Epub 2020 Mar 24.

Department of Neurosurgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.

Despite the remarkable advances in critical care management of acute brain injury for the past 20 years, the prognoses remain poor. However, numerous reports indicate the efficacy of Traditional Chinese Medicine (TCM) therapy in stroke rehabilitation. This study aimed to determine the efficacy and safety of integrated TCM (Wendan decoction [WDD]) in patients with acute brain injury as a combination therapy in the early stages. Prospective randomized controlled trial. Single-center study. Sixty patients diagnosed with acute brain injury were randomly assigned to intervention and control groups, equally, and 41 patients completed the study. All patients were treated by conventional neurologic intensive care. The 23 patients in the intervention group were administered with an integrated WDD in the early stages three times daily; combination treatment was initiated within 14 days and lasted >1 month. Duration of ventilator use, intensive care unit stays, Glasgow Coma Scale (GCS) scores, motor response, the best muscle power, disability rating scale (DRS) scores, modified Rankin scale (mRS) scores, and the mortality rate for the first month. The other outcome measures were GCS scores, motor response, the best muscle power, DRS, mRS, and Barthel index (BI) scores 6 months later. There was no mortality in the intervention group, but the rate was 39% in the control group for first month. Comparisons between groups showed significant differences ( < 0.05) in GCS, DRS, mRS, and BI scores, indicating improvements in the intervention group after 6 months. In the early stages of acute brain injury, combination treatment with WDD was found to be safe. Furthermore, this treatment may improve neurologic functional outcomes after 6 months.
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http://dx.doi.org/10.1089/acm.2019.0349DOI Listing
May 2020

The effectiveness of a health promotion intervention on the meaning of life, positive beliefs, and well-being among undergraduate nursing students: One-group experimental study.

Medicine (Baltimore) 2020 Mar;99(10):e19470

Department of Education, National Taipei University of Education, Taipei, Taiwan, ROC.

Nursing educators have a responsibility to value undergraduate nursing students' physical, psychological, spiritual, and social health promotion.The purpose of the study was to examine the effectiveness of a health promotion intervention concerning meaning of life, positive beliefs, and well-being among undergraduate nursing students in a health promotion curriculum.The study was adopted a pretest, posttest, and post post-test design in 1-group experimental study with a purposive sample of 112 undergraduate nursing students who attended in a health promotion curriculum and voluntarily completed a reliable 3-part questionnaire (content validity index = 0.95; Cronbach's αs = meaning of life, 0.97; positive beliefs, 0.94; and well-being 0.96).Undergraduate nursing students showed significant (all P < .001) improvements on the meaning of life, positive beliefs, and well-being immediately after the intervention, which were sustained over time.Nursing educators should incorporate these variables into the health promotion curriculum to enhance undergraduate nursing students' physical, psychological, spiritual, and social health promotion.
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http://dx.doi.org/10.1097/MD.0000000000019470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478399PMC
March 2020

Factors associated with post-partum smoking relapse in Taiwan: A trial of Smoker's helpline.

Taiwan J Obstet Gynecol 2019 Sep;58(5):667-672

Department of Education and Research, Taipei City Hospital, Taipei, Taiwan; Institute of Public Health & Department of Public Health, National Yang Ming University, Taipei, Taiwan.

Objective: Many women quit smoking during pregnancy resume in postpartum period and difficult to prevent. No studies had focused on their psychosocial response in Taiwan. We analyzed data from a trial of Taiwan Smoker's Helpline (TSH) to determine factors associated with smoking relapse after delivery.

Materials And Methods: A prospective cohort was conducted at Taipei City Hospital during Sep. 2014 and Nov. 2015 period. We collected data by self-developed questionnaire combining theory of planned behavior (TPB), Fagerstrom test for nicotine dependence (FTND) and Edinburgh Postnatal Depression Scale (EPDS) from 68 women immediately after delivery, 2 months later and followed up until 6 months. Multivariable logistic models for relapse of smoking at the end of 3rd month and 6th month were created.

Results: At 6th month, 42.6% participants relapsed with odds lower among first parity (OR = 0.04, 95% CI = <0.01-0.54, p = 0.015), having quitting experience in past (OR = 0.09, 95% CI = 0.01-0.84, p = 0.019) and higher perceived behavior control (PBC) (OR = 0.99, 95% CI = 0.98-1.00, p = 0.035), but greater for those with longer smoking duration in past (OR = 1.29, 95% CI = 1.04-1.58, p = 0.018).

Conclusion: Protective and precipitating factors to post-partum's smoking relapse were identified in our study.
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http://dx.doi.org/10.1016/j.tjog.2019.07.015DOI Listing
September 2019

Adult-onset leukoencephalopathy, cerebral calcifications, and cysts: An 8-year neuroimaging follow-up of disease progression and histopathological correlation.

J Clin Neurosci 2019 Nov 22;69:276-279. Epub 2019 Aug 22.

Department of Medical Imaging, Taipei Medical University Hospital, Taiwan; Translational Imaging Research Center, College of Medicine, Taipei Medical University, Taiwan.

Leukoencephalopathy, cerebral calcifications, and cysts (LCC) is an extremely rare neurological disease, also known as Labrune syndrome. The disease more commonly affects children and young adults and the characteristic triple imaging findings are leukoencephalopathy, calcifications and multiple cysts, presenting with a variety of supra- and infratentorial symptoms but lacking for extra-neurological manifestations. Coats plus syndrome and cerebroretinal microangiopathy with calcifications and cysts (CRMCC) share similar neurological findings with LCC, but additionally involves other extra-neurological organs. Tumoral excision is usually required due to mass effect to the eloquent brain of multiple growing cysts or hemorrhages, but the outcome of surgery varies. Here we demonstrate an 8-year neuroimaging study of a rare adult-onset case of LCC with gradual headache, hemiparesis, hand tremors, unstable gait, and seizure attacks despite several times of tumoral excision. Neuroimaging revealed multiple microbleeds and microcalcification in the leukoencephalopathic areas, with increasing calcifications, recurrent previously excised cysts and new cyst formation in the longitudinal neuroimaging follow-ups within the eight years. We believe that LCC involves microangiopathy, which causes blood-brain barrier disruption, myelin serum collection and subsequent growing cysts and dystrophic calcification formation. We provide histopathological correlation in the illustration. Due to the underlying pathomechanism and long-term recurrence nature, patients with a combination of cysts and calcifications on CT scan should be follow up carefully and postoperative recurrence after years may occur.
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http://dx.doi.org/10.1016/j.jocn.2019.08.006DOI Listing
November 2019

Immuohistochemical score of matrix metalloproteinase-1 may indicate the severity of symptomatic cervical and lumbar disc degeneration.

Spine J 2020 01 11;20(1):124-137. Epub 2019 Aug 11.

School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan. Electronic address:

Background Context: Intervertebral disc (IVD) degeneration is related to numerous risk factors, including obesity. Leptin, one of the commonly measured adipokines, is proven to play an important role in the pathogenesis of IVD degeneration. In the context of IVD degeneration, matrix metalloproteinase-1 (MMP-1), which is upregulated and activated by leptin, is the most abundant catabolic enzyme. It remains unclear which of the factors mentioned above is most strongly associated with IVD degeneration.

Purpose: To investigate the influence of MMP-1 in IVD degeneration, we determined the strength of different predictors, including age, sex, magnetic resonance imaging (MRI), Modic changes (MCs), body mass index (BMI), leptin, and MMP-1. This was achieved by assessing the correlation among these factors and histologic degeneration score (HDS).

Study Design: This study included 89 patients undergoing cervical discectomy for disc herniation, 93 who underwent lumbar discectomy, and 90 control subjects. Herniated disc tissue and plasma were used after the study was approved by the Human Ethics Review Committee at the authors' institution.

Methods: Hematoxylin and eosin (H&E), Alcian blue-PAS and immunohistochemical (IHC) staining were performed to measure the expression levels of leptin and MMP-1. Circulating plasma levels of leptin and MMP-1 were measured using an enzyme-linked immunosorbent assay. To assess the correlation with HDS, measurements of age, sex, BMI, MRI scale, MCs scale, leptin/MMP-1 plasma concentration, and leptin/MMP-1 IHC expression were analyzed.

Results: Patients with cervical or lumbar discectomy had significantly higher BMI than controls. Significantly more men than women were involved in the lumbar patients as compared with the cervical patients and the control subjects. After adjustment for age and sex, plasma leptin and leptin IHC score correlated significantly with BMI in patients with cervical or lumbar discectomy. Age, sex, MRI scale, MCs scale, and leptin/MMP-1 plasma concentration were not positively correlated with HDS. HDS was significantly associated with BMI, leptin IHC score, and MMP-1 IHC score. After a stepwise-multiple linear regression analysis to evaluate the strength of the correlations between HDS and various factors, only the MMP-1 IHC score demonstrated an independent association with HDS in patients with degeneration of the cervical or lumbar disc.

Conclusions: MMP-1 IHC score is an independent predictor of the severity of cervical or lumbar IVD degeneration.

Clinical Significance: MMP-1 IHC score may be used as an indicator of IVD degeneration.
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http://dx.doi.org/10.1016/j.spinee.2019.08.004DOI Listing
January 2020