Identification of prothymosin alpha (PTMA) as a biomarker for esophageal squamous cell carcinoma (ESCC) by label-free quantitative proteomics and Quantitative Dot Blot (QDB).

BACKGROUND: Esophageal cancer (EC) is one of the malignant tumors with a poor prognosis. The early stage of EC is asymptomatic, so identification of cancer biomarkers is important for early detection and clinical practice. METHODS: In this study, we compared the protein expression profiles in esophageal squamous cell carcinoma (ESCC) tissues and adjacent normal esophageal tissues from five patients through high-resolution label-free mass spectrometry. Through bioinformatics analysis, we found the differentially expressed proteins of ESCC. To perform the rapid identification of biomarkers, we adopted a high-throughput protein identification technique of Quantitative Dot Blot (QDB). Meanwhile, the QDB results were verified by classical immunohistochemistry. RESULTS: In total 2297 proteins were identified, out of which 308 proteins were differentially expressed between ESCC tissues and normal tissues. By bioinformatics analysis, the four up-regulated proteins (PTMA, PAK2, PPP1CA, HMGB2) and the five down-regulated proteins (Caveolin, Integrin beta-1, Collagen alpha-2(VI), Leiomodin-1 and Vinculin) were selected and validated in ESCC by Western Blot. Furthermore, we performed the QDB and IHC analysis in 64 patients and 117 patients, respectively. The PTMA expression was up-regulated gradually along the progression of ESCC, and the PTMA expression ratio between tumor and adjacent normal tissue was significantly increased along with the progression. Therefore, we suggest that PTMA might be a potential candidate biomarker for ESCC. CONCLUSION: In this study, label-free quantitative proteomics combined with QDB revealed that PTMA expression was up-regulated in ESCC tissues, and PTMA might be a potential candidate for ESCC. Since Western Blot cannot achieve rapid and high-throughput screening of mass spectrometry results, the emergence of QDB meets this demand and provides an effective method for the identification of biomarkers.

PDLIM5 identified by label-free quantitative proteomics as a potential novel biomarker of papillary thyroid carcinoma.

In order to better understand the mechanisms underlying the development of papillary thyroid carcinoma (PTC), and to identify new potential biomarkers, high-resolution label-free mass spectrometry was performed on PTC tissues and adjacent normal thyroid tissues from six patients. In this process, 2788 proteins were identified, out of which 49 proteins presented significant differences between PTC tissues and adjacent normal thyroid tissues. Gene ontology revealed that the majority of these proteins are involved in the catalytic activity and binding. We selected three proteins with differential expressions: PDZ and LIM domain 5 (PDLIM5), PDLIM1 and ALDH1A1; Protein expressions were further verified by RT-PCR and western blot. Among these, expression of PDLIM5 and PDLIM1 was up-regulated, while that of ALDH1A1 was down-regulated in PTC tissues. Next, we confirmed their expression through quantitative dot blot (QDB) technique. We found that knockdown of PDLIM5 expression in the B-CPAP cell line could inhibit the migration, invasion and proliferation of PTC cells. In addition, PDLIM5 knockdown reduced Ras and Phospho-ERK1/2 expression. Thus, we suggested that PDLIM5 promotes PTC via activation of the Ras-ERK pathway. Our research provides new molecular insight into the function of PDLIM5, which may assist in studying the mechanism of PTC. In addition, PDLIM5 could be further explored as a potential candidate for PTC treatment.

Locoregional control of recurrent papillary thyroid carcinoma by ultrasound-guided percutaneous microwave ablation: A prospective study.

PURPOSE: The aim of this study was to evaluate the safety and efficiency of ultrasound-guided percutaneous microwave (MW) ablation for the control of locally recurrent papillary thyroid carcinoma (LR-PTC) in patients for whom surgery is not viable. MATERIALS AND METHODS: The inclusion criteria for MW ablation were three or fewer LR-PTCs and no recurrence beyond the neck, with ineligibility or refusal to undergo surgery. MW ablation was carried out using a 16-gauge MW antenna under local anaesthesia. Patients were then followed at 1, 3, 6 and 12 months after treatment and every 6 months thereafter. Technical success usually meant volume reduction more than 50%. RESULTS: Between October 2010 to March 2013 a total of 17 patients (14 women, 3 men; average age 54.1 years) with 23 LR-PTCs, were treated with MW ablation in our department. All the LR-PTCs were technical successes with the number of treatment sessions for one tumour ranging from 1 to 4 (mean, 2.3 ± 0.9). The mean volume reduction ratio of the LR-PTCs was 1 ± 86%, 47 ± 12%, 70 ± 33%, 91 ± 14% at the 1, 3, 6 and 18 months follow-up visit respectively (all p < 0.05). All treated nodules decreased in size: 30.4% nodules (7/23) had completely disappeared, 52.2% nodules (12/23) remained as small scar-like lesions. One patient experienced transient dysphonia immediately after MW ablation. No other severe and permanent complications occurred. CONCLUSION: Although with some limitations, our preliminary results are encouraging and show MW ablation may be an alternative treatment option for the control of LR-PTCs in selected patients for whom surgery is not viable.

Ultrasound-guided percutaneous microwave ablation of solitary T1N0M0 papillary thyroid microcarcinoma: initial experience.

PURPOSE: The aim of this study was to evaluate the feasibility, safety and efficacy of ultrasound-guided percutaneous microwave (MW) ablation for solitary T1N0M0 papillary thyroid microcarcinoma. MATERIALS AND METHODS: A total of 21 patients (six men and 15 women; age range, 29-81 years; mean, 52.1 ± 13.6 years) with 21 nodules of pathologically proven solitary papillary carcinoma 3.7 to 10.0 mm in diameter without clinically apparent lymph node, or distant metastasis at diagnosis (T1N0M0) were treated with MW ablation in our department. Microwaves were emitted at 40 W for 400 s and prolonged as necessary to attain confluent ablation zones. All patients were treated with levothyroxine after MW ablation to maintain thyroid stimulating hormone (TSH) levels below 0.1 mU/L. Follow-up consisted of ultrasound in 21 patients, biopsy in five patients, and surgical treatment in three patients. RESULTS: Four patients complained of hoarseness immediately after the MW ablation procedure, and all of them recovered within 3 months spontaneously. All tumours were completely ablated at a single session and no serious or permanent complications occurred. No recurrence at the treatment site and no distant metastases were detected, with a mean follow-up of 11 months. Histological examination showed no evidence of a tumour in the treated lesions in eight patients. Follow-up ultrasound examinations showed disappearance of previously detected colour Doppler flow, as well as mass shrinkage, or both. CONCLUSION: During the short-term follow-up period, ultrasound-guided percutaneous MW ablation appears to be a safe and effective technique for solitary T1N0M0 papillary thyroid microcarcinoma.

Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia.

The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer's disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types. Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes, including upregulation of pathways related to phagocytosis and immunity. Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc, but not Fab, fragment. Our data indicate that microglia, when exposed to gamma-type immunoglobulin, exhibit an enhanced capacity for clearing amyloid-beta fibrils, potentially via the gamma-type immunoglobulin Fc fragment signaling pathway. This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer's disease by enhancing microglial function.

A Self-powered Neural Stimulator Based on Programmable Triboelectric Nanogenerators.

Modulation of peripheral nerve is an emerging field for neuroprosthesis and bioelectronic medicine. With the developing neural interfacing technology that directly communicates with peripheral nerves, several powering schemes have been investigated for long-term use of implantable devices such as wireless and conversion of human body energy. But due to the limitations such as energy conversion efficiency and complexity, none of these methods can fully replace the current battery-based neuroprosthetic systems. This study proposes a new scheme based on programmable triboelectric nanogenerators for self-powered neural stimulations. The device can generate current pulses of more than 100 V by slightly shaking the device. The capability of neural stimulation is validated by sciatic nerve stimulation. Furthermore, the shaking frequency can control the measured kicking force of the rat leg. This prototype can be further minimized and optimized for a fully implantable self-powered/wireless neuroprosthetic system.

The effect of the subthreshold oscillation induced by the neurons' resonance upon the electrical stimulation-dependent instability.

Repetitive electrical nerve stimulation can induce a long-lasting perturbation of the axon's membrane potential, resulting in unstable stimulus-response relationships. Despite being observed in electrophysiology, the precise mechanism underlying electrical stimulation-dependent (ES-dependent) instability is still an open question. This study proposes a model to reveal a facet of this problem: how threshold fluctuation affects electrical nerve stimulations. This study proposes a new method based on a Circuit-Probability theory (C-P theory) to reveal the interlinkages between the subthreshold oscillation induced by neurons' resonance and ES-dependent instability of neural response. Supported by in-vivo studies, this new model predicts several key characteristics of ES-dependent instability and proposes a stimulation method to minimize the instability. This model provides a powerful tool to improve our understanding of the interaction between the external electric field and the complexity of the biophysical characteristics of axons.

Nanocone-Array-Based Platinum-Iridium Oxide Neural Microelectrodes: Structure, Electrochemistry, Durability and Biocompatibility Study.

Neural interfaces provide a window for bio-signal modulation and recording with the assistance of neural microelectrodes. However, shrinking the size of electrodes results in high electrochemical impedance and low capacitance, thus limiting the stimulation/recording efficiency. In order to achieve critical stability and low power consumption, here, nanocone-shaped platinum (Pt) with an extensive surface area is proposed as an adhesive layer on a bare Pt substrate, followed by the deposition of a thin layer of iridium oxide (IrOx) to fabricate high-performance nanocone-array-based Pt-IrOx neural microelectrodes (200 µm in diameter). A uniform nanocone-shaped Pt with significant roughness is created via controlling the ratio of NH4+ and Pt4+ ions in the electrolyte, which can be widely applicable for batch production on multichannel flexible microelectrode arrays (fMEAs) and various substrates with different dimensions. The Pt-IrOx nanocomposite-coated microelectrode presents a significantly low impedance down to 0.72 ± 0.04 Ω cm2 at 1 kHz (reduction of ~92.95%). The cathodic charge storage capacity (CSCc) and charge injection capacity (CIC) reaches up to 52.44 ± 2.53 mC cm-2 and 4.39 ± 0.36 mC cm-2, respectively. Moreover, superior chronic stability and biocompatibility are also observed. The modified microelectrodes significantly enhance the adhesion of microglia, the major immune cells in the central nervous system. Therefore, such a coating strategy presents great potential for biomedical and other practical applications.

A physical perspective to understand myelin. I. A physical answer to Peter's quadrant mystery.

In the development of oligodendrocytes in the central nervous systems, the inner and outer tongue of the myelin sheath tend to be located within the same quadrant, which was named as Peters quadrant mystery. In this study, we conduct in silico investigations to explore the possible mechanisms underlying the Peters quadrant mystery. A biophysically detailed model of oligodendrocytes was used to simulate the effect of the actional potential-induced electric field across the myelin sheath. Our simulation suggests that the paranodal channel connecting the inner and outer tongue forms a low impedance route, inducing two high-current zones at the area around the inner and outer tongue. When the inner tongue and outer tongue are located within the same quadrant, the interaction of these two high-current-zones will induce a maximum amplitude and a polarity reverse of the voltage upon the inner tongue, resulting in the same quadrant phenomenon. This model indicates that the growth of myelin follows a simple principle: an external negative or positive E-field can promote or inhibit the growth of the inner tongue, respectively.

A physical perspective to understand myelin II: The physical origin of myelin development.

The physical principle of myelin development is obtained from our previous study by explaining Peter's quadrant mystery: an externally applied negative and positive E-field can promote and inhibit the growth of the inner tongue of the myelin sheath, respectively. In this study, this principle is considered as a fundamental hypothesis, named Hypothesis-E, to explain more phenomena about myelin development systematically. Specifically, the g-ratio and the fate of the Schwann cell's differentiation are explained in terms of the E-field. Moreover, an experiment is proposed to validate this theory.

Internal Jugular Vein Thrombosis After Microwave Ablation of Cervical Lymph Node Metastasis in Papillary Thyroid Microcarcinoma: A Case Report.

In this study, two patients with papillary thyroid carcinoma and lymph node metastasis were treated by Dr. Shurong Wang's team and are reported. The two patients refused surgery and underwent microwave ablation (MWA) of the thyroid and lymph node lesions. Ultrasound review 2 days after MWA revealed internal jugular vein thrombosis. Patient #1 received low molecular weight heparin calcium injection, Xueshuantong injection, Xiangdan injection, and rivaroxaban. Patient #2 was treated with enoxaparin sodium injection, Xueshuantong injection, urokinase, and warfarin sodium tablet. The thrombus was successfully managed in each patient using anticoagulant treatment. Such complication of MWA has not been reported in many cases before. According to the relevant literature, thrombosis after thyroid cancer ablation might be related to subclinical hypothyroidism, increased heme oxidase 1 (HO-1) levels in the blood of patients with papillary thyroid cancer, and increased platelet content and mean platelet volume in patients with thyroid cancer. No specific cause of thrombosis was identified in the two cases reported here. No recurrence was observed after 1 (patient #1) and 4 (#2) years of follow-up. In conclusion, patients with papillary thyroid carcinoma and lymph node metastasis should undergo color Doppler ultrasound of the neck after MWA of thyroid lesions and neck metastasis.

A Meta-Analysis on the Association Between TNFSF4 Polymorphisms (rs3861950 T > C and rs1234313 A > G) and Susceptibility to Coronary Artery Disease.

Background: Coronary artery disease (CAD) remains the leading cause of mortality worldwide, and its susceptibility is closely associated with genetic modifications. The association between inflammation and CAD has been investigated in detail. This meta-analysis was conducted based on the PRISMA guidelines to evaluate the association between the tumor necrosis factor superfamily member 4 (TNFSF4) gene polymorphisms (rs3861950 T > C and rs1234313 A > G) and the risk of CAD. Methods: The selected criteria included 11 eligible articles containing 18 studies (nine studies included 7,395 cases and 5,296 controls for rs3861950 and nine studies with 6,951 cases and 4,959 controls for rs1234313). Correlations between the two polymorphisms and CAD were estimated by pooling the odds ratios (ORs) with 95% confidence interval (95% CI) in allelic, dominant, recessive, heterozygous, and homozygous models. Results: The pooled analyses demonstrated that the rs3861950 T > C polymorphism was significantly associated with an increased risk of CAD in the Asian population in the allelic model, dominant model, and homozygous model. Furthermore, subgroup analysis based on disease type showed that TNFSF4 rs3861950 T > C had a robust correlation with increased risk of cerebral infarction (CI) in the allelic model, dominant model, heterozygous model, and homozygous model. However, the rs1234313 A > G polymorphism mostly tended to decrease the risk of CAD in the Asian and Caucasian populations in the allelic and dominant model. This single nucleotide polymorphism (SNP) had a close relation to myocardial infarction (MI) susceptibility in the allelic model, dominant model, and heterozygous model. Conclusion: This meta-analysis identified two novel SNPs in TNFSF4 significantly associated with CAD susceptibility.

US-guided Microwave Ablation of Low-Risk Papillary Thyroid Microcarcinoma: Longer-Term Results of a Prospective Study.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) has become a main cause of the extremely high incidence of thyroid carcinoma. This study aimed to evaluate the longer-term effectiveness of ultrasound (US)-guided microwave ablation (MWA) for treatment of low-risk PTMC with a large population. METHODS: This prospective study was approved by ethics committee of our institution. MWA was performed under US-guidance for 119 unifocal PTMC patients without clinically cervical or distant metastasis. The target ablation zone exceeded the tumor edge judged by contrast-enhanced US to avoid marginal residue and recurrence. US and thyroid function evaluation were followed at 1, 3, 6, and 12 months after treatment and every 6 to 12 months thereafter. Any adverse event associated with MWA was evaluated. RESULTS: The follow-up duration after MWA was 37.2 ± 20.9 months (range 12-101 months). Tumor volume decreased significantly from 1.87 ± 1.03 mL immediately after MWA to 0.01 ± 0.04 mL at the final evaluation (P < 0.001), with a mean volume reduction ratio of 99.4 ± 2.2% and 107 cases (93.9%) got complete remission. A patient was detected with cervical lymph node metastasis at 26-month follow-up and underwent 1 additional MWA treatment successfully. No distant metastasis was observed. All the acquired histological pathology results confirmed the absence of residual or recurrent tumor cells after MWA. No delayed complications associated with MWA were encountered for all patients. CONCLUSIONS: Percutaneous MWA is technically feasible for complete PTMC destruction and showed well longer-term effectiveness; thus, it seems to be an effective nonsurgical therapy to complement the current recommendation for selected low-risk PTMC patients.

Ultrasound guided percutaneous microwave ablation of benign thyroid nodules: safety and imaging follow-up in 222 patients.

OBJECTIVE: Microwave ablation is a minimally invasive technique that has been used to treat benign and malignant tumors of liver, lung and kidney. Towards thyroid nodules, only a few cases are reported so far. The aim of the study was to investigate the effectiveness and safety of ultrasound-guided percutaneous microwave ablation in the treatment of benign thyroid nodules with a large sample. MATERIALS AND METHODS: A total of 477 benign thyroid nodules in 222 patients underwent microwave ablation in our department from July 2009 to March 2012. Microwave ablation was carried out using microwave antenna (16G) under local anesthesia. Nodule volume, thyroid function and clinical symptoms were evaluated before treatment and at 1, 3, more than 6 months. The study was ethics committee approved and written informed consents were obtained from all patients. RESULTS: All thyroid nodules significantly decreased in size after microwave ablation. A 6-month follow-up was achieved in 254 of 477 nodules, and the mean decrease in the volume of thyroid nodules was from 2.13 ± 4.42 ml to 0.45 ± 0.90 ml, with a mean percent decrease of 0.65 ± 0.65. A volume-reduction ratio greater than 50% was observed in 82.3% (209/254) of index nodules, and 30.7% (78/254) of index nodules disappeared 6-month after the ablation. The treatment was well tolerated and no major complications were observed except pain and transient voice changes. CONCLUSIONS: Microwave ablation seems to be a safe and effective technique for the treatment of benign thyroid nodules. Further prospective randomized studies are needed to define the role of the procedure in the treatment of thyroid nodules.