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Background: Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer globally, with average age of cancer patients becoming younger gradually. It is of significance to gain a comprehensive understanding of molecular mechanism underlying NSCLC.Methods: Quantitative polymerase chain reaction (qPCR) and western blot were applied to measure RNA and protein levels separately. Functional assays and western blot were performed to determine the effects of miR-489-3p and USP48 on cell growth, migration and epithelial-mesenchymal transition (EMT) in NSCLC. TOP/FOP flash luciferase reporter assay was carried out to detect the activity of Wnt pathway. Besides, qPCR, RNA pulldown and luciferase reporter assays were conducted to probe into the target gene of miR-489-3p. Immunoprecipitation-western blot (IP-western blot) analysis was implemented to assess the effect of USP48 on the ubiquitination of β-catenin.Results: miR-489-3p hampers NSCLC cell proliferation, migration and EMT in vitro and NSCLC tumorigenesis and metastasis in vivo. Additionally, miR-489-3p inactivates Wnt/β-catenin signaling pathway and regulates USP48 to inhibit the ubiquitination of β-catenin. Moreover, USP48 propels the development of NSCLC cells.Conclusions: The current study demonstrated that miR-489-3p promotes the malignant progression of NSCLC cells via targeting USP48, which might offer a new perspective into NSCLC treatment. [ABSTRACT FROM AUTHOR]

Background: In acupuncture practice, the most important step is to confirm the location of a sensitized acupoint which reflects a diagnosis and can be stimulated with a specialized needle to treat the disease. Abnormal symptoms such as hyperalgesia or allodynia at the sensitized acupoints in patients with visceral disorders are considered to be in relation with referred pain and neurogenic inflammation. Yet, limited study has investigated the cutaneous neurochemical changes of the sensitized acupoints. Methods: The resent study developed an animal model of gastric mucosal injury (GMI) by HCl administered into the stomach of the rats. Evans Blue (EB) dye was applied by injection of tail vein after mucosal damage to observe the neurogenic plasma extravasation dots in the skin of the rats. The EB dots extravagated in the skin were compared with locations of acupoints. Immnohistochemistry analysis was used to detect the expression of calcitonin gene-related peptide (CGRP)- or substance P (SP)-labeled nerve fibers, histamine (HA)-, serotonin (5-HT)-, and tryptase-labeled cells in EB dots. Images were recorded and analyzed by Confocal imaging system and Olympus Image Processing Software. Results: The results showed that GMI resulted in neurogenic plasma extravasation in the skin of the acupoints over the back and abdomen, which mostly occurred in the T9-11 dermatomere. The EB extravasation dots appeared after GMI and disappeared gradually during the natural self-recovery of the gastric mucosa. More SP and CGRP positive nerve fibers were distributed in EB dots than that in regions beside EB dots and in the control, mostly distributed in the nerve fibers around both the vessels and root of hair follicle. Mast cells also aggregated and degranulated to release algogenic substances of 5-HT and HA around the vessels in areas of the EB dots. Conclusions: Our results indicates that the mechanism of EB extravasation in the skin of the acupoints induced by GMI are closely related to neurogenic inflammation, and that the high expression of local allergic substances and nociceptive neuropeptides in the local skin including SP, CGRP, HA, 5-HT, and mast cell tryptase may be the underlying mechanism of the acupoint sensitization. [ABSTRACT FROM AUTHOR]

Background: Biohythane production via two-stage fermentation is a promising direction for sustainable energy recovery from lignocellulosic biomass. However, the utilization of lignocellulosic biomass suffers from specific natural recalcitrance. Hydrothermal liquefaction (HTL) is an emerging technology for the liquefaction of biomass, but there are still several challenges for the coupling of HTL and two-stage fermentation. One particular challenge is the limited efficiency of fermentation reactors at a high solid content of the treated feedstock. Another is the conversion of potential inhibitors during fermentation. Here, we report a novel strategy for the continuous production of biohythane from cornstalk through the integration of HTL and two-stage fermentation. Cornstalk was converted to solid and liquid via HTL, and the resulting liquid could be subsequently fed into the two-stage fermentation systems. The systems consisted of two typical high-rate reactors: an upflow anaerobic sludge blanket (UASB) and a packed bed reactor (PBR). The liquid could be efficiently converted into biohythane via the UASB and PBR with a high density of microbes at a high organic loading rate. Results: Biohydrogen production decreased from 2.34 L/L/day in UASB (1.01 L/L/day in PBR) to 0 L/L/day as the organic loading rate (OLR) of the HTL liquid products increased to 16 g/L/day. The methane production rate achieved a value of 2.53 (UASB) and 2.54 L/L/day (PBR), respectively. The energy and carbon recovery of the integrated HTL and biohythane fermentation system reached up to 79.0 and 67.7%, respectively. The fermentation inhibitors, i.e., 5-hydroxymethyl furfural (41.4-41.9% of the initial quantity detected) and furfural (74.7-85.0% of the initial quantity detected), were degraded during hydrogen fermentation. Compared with single-stage fermentation, the methane process during two-stage fermentation had a more efficient methane production rate, acetogenesis, and COD removal. The microbial distribution via Illumina MiSeq sequencing clarified that the biohydrogen process in the two-stage systems functioned not only for biohydrogen production, but also for the degradation of potential inhibitors. The higher distribution of the detoxification family Clostridiaceae, Bacillaceae, and Pseudomonadaceae was found in the biohydrogen process. In addition, a higher distribution of acetate-oxidizing bacteria (Spirochaetaceae) was observed in the biomethane process of the two-stage systems, revealing improved acetogenesis accompanied with an efficient conversion of acetate. Conclusions: Biohythane production could be a promising process for the recovery of energy and degradation of organic compounds from hydrothermal liquefied biomass. The two-stage process not only contributed to the improved quality of the gas fuels but also strengthened the biotransformation process, which resulted from the function of detoxification during biohydrogen production and enhanced acetogenesis during biomethane production. [ABSTRACT FROM AUTHOR]

Background: Hsp90 proteins are important therapeutic targets for many anti-cancer drugs in clinical trials. Geldanamycin (GA) was identified as the first natural inhibitor of Hsp90, increasing evidence suggests that GA was not a good choice for clinical trials. In this study, we investigated two new non-benzoquinone geldanamycin analogs of Hsp90 inhibitors, DHQ3 and 17-demethoxy-reblastatin (17-DR), to explore the molecular mechanisms of their anti-cancer activity in vivo and vitro. Methods: MTT and colony formation assays were used to measure cell viability. Flow cytometry, DAPI staining, ATP assay, electron microscopy, western blots, siRNAs transfection and immunofluorescence were used to determine the molecular mechanism of DHQ3- or 17-DR-induced different forms of death in human breast cancer MDA-MB-231 cells. Malachite green reagent was used to measure ATPase activity of the analogs. Results: DHQ3 and 17-DR presented efficiently inhibitory effect in MDA-MB-231 cell lines, and DHQ3 induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade. And DHQ3-induced cell death was inhibited by a necroptosis inhibitor, necrostatin-1 (Nec-1), but not by a caspase inhibitor z-VAD-fmk. On the other hand, 17-DR induced apoptosis in MDA-MB-231 cells, indicating a caspase-dependent killing mechanism. We further demonstrated that down-regulation of RIP1 and RIP3 by siRNA protected against DHQ3 but not 17-DR induced cell death. These results were confirmed by electron microscopy. DHQ3 and 17-DR induced the degradation of Hsp90 client proteins, and they showed strong antitumor effects in MDA-MB-231 cell-xenografted nude mice. Conclusions: These findings supported that DHQ3 and 17-DR induce different forms of death in some cancer cell line via activation of different pathways. All of the results provided evidence for its anti-tumorigentic action with low hepatotoxicity in vivo, making them promising anti-breast cancer agents. [ABSTRACT FROM AUTHOR]

Background: Chemokines have been recognized as important modulators of angiogenesis, and they play critical roles in the development and metastasis of hepatocellular carcinoma (HCC), although their origins and latent molecular mechanisms remain elusive. The aim of this study was to investigate how activated hepatic stellate cells (a-HSCs) promote angiogenesis in HCC.Methods: A total of 22 HCC patients were enrolled randomly. We used immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay (ELISA) to analyse the production of interleukin-8 (IL-8) in a-HSCs derived from HCC tissues. The angiogenic effects of IL-8 in vitro and in vivo were assessed by ELISA, real-time quantitative polymerase chain reaction, capillary tube formation assay, and chick embryo chorioallantoic membrane assay.Results: The present study showed that IL-8 was enriched predominantly in the tumour stroma of HCC tissues and was mainly derived from a-HSCs, rather than from hepatoma cells, in vivo and in vitro. Angiogenesis was most active at the invading edge, which was close to the a-HSCs. The angiogenic effect was dramatically attenuated by an IL-8 neutralizing antibody both in vitro and in vivo. Moreover, the IL-8 neutralizing antibody down-regulated Ser727-phosphorylated STAT3 levels in hepatoma cells treated with a-HSCs conditioned medium.Conclusions: These findings reveal that a-HSCs within the stroma of HCC contribute to tumour angiogenesis via IL-8. [ABSTRACT FROM AUTHOR]

Background: In Chinese medicine, dual effects on target organs are considered a primary characteristic of acupoint. Acupoints may be classified as heterotopic or homotopic in terms of spinal segmental innervation: homotopic acupoints contain afferent innervation in the same segment from which efferent fibers innervate target visceral organs, and heterotopic acupoints utilize different spinal segments to innervate target visceral organs than the segment receiving the afferent signal. It is well-known that dual effects of acupuncture on the bladder can be generated based on different states of the bladder, however, the dual effects of single acupoint stimulation and acupoint site-specificity (homotopic acupoints and heterotopic acupoints) on the bladder have yet to be investigated. Methods: Twenty Sprague-Dawley rats were anesthetized and the intravesical pressure was measured via a manometric balloon inserted into the bladder. The acupuncture needle was separately inserted to a depth of 4 mm at the acupoints RN1 (Huiyin), RN3 (Zhongji), BL28 (Pangguangshu), BL32 (Ciliao), RN2 (Qugu) or BL23 (Shenshu), and manually rotated right then left with a frequency of 2 Hz for 1 min. Following acupuncture stimulation, bladder pressure was recorded and compared against the pre-stimulation measurements. Results: During the bladder's active state, manual acupuncture (MA) at RN1, RN3, BL28, BL32 or RN2 inhibited bladder motility (P < 0.01). In the static bladder, MA at RN1, RN3, BL28, BL32, RN2 or BL23 increased bladder motility (P < 0.01). Conclusions: MA at homotopic acupoints may produce dual effects on bladder motility: inhibiting bladder motility when in an active state and enhancing bladder motility when in a static state. [ABSTRACT FROM AUTHOR]

Background: Recently, clinical observations reported the potential benefit of vagus nerve stimulation (VNS) for pediatric epilepsy. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a newer non-invasive VNS, making it more accessible for treating pediatric epilepsy, yet there is limited clinical evidence for its effectiveness. Methods/Design: A three-center, randomized, parallel, controlled trial will be carried out to evaluate whether ta-VNS improves pediatric epilepsy. Pediatric patients aged 2 to 14 years with epilepsy will be recruited and randomly assigned to transcutaneous auricular vagus nerve stimulation (ta-VNS) group, transcutaneous auricular non-vagus nerve stimulation (tan-VNS) group, and control group with a 1:1: sqrt(2) allocation, as per a computer generated randomization schedule stratified by study center using permuted blocks of random sizes. We will use Zelen's design, in which randomization occurs before informed consent. Patients in the stimulation groups will receive tan-VNS or ta-VNS three times a day for 6 months. Patients in the control group will not be provided with any stimulation during the 6 months. The guardians of the patients are required to keep a detailed diary to record the data. Outcome assessment including seizure frequency, electroencephalogram (EEG), heart rate variability (HRV) analysis, quality of life (QOL) and adverse events will be made at baseline and 2, 4 and 6 months after ta-VNS initiation. The seizure frequency and adverse events will be followed up at 1 year and 1.5 years after ta-VNS initiation. Discussion: Results of this trial will help clarify whether ta-VNS treatment is beneficial for pediatric patients, and will make clear whether the anticonvulsive effect of ta-VNS is correlated with the improvement of sympathovagal imbalance. [ABSTRACT FROM AUTHOR]

Background: The Malaysian giant freshwater prawn, Macrobrachium rosenbergii, is an economically important crustacean worldwide. However, production of this prawn is facing a serious threat from Vibriosis disease caused by Vibrio species such as Vibrio parahaemolyticus. Unfortunately, the mechanisms involved in the immune response of this species to bacterial infection are not fully understood. We therefore used a high-throughput deep sequencing technology to investigate the transcriptome and comparative expression profiles of the hepatopancreas from this freshwater prawn infected with V. parahaemolyticus to gain an increased understanding of the molecular mechanisms underlying the species' immune response to this pathogenic bacteria. Result: A total of 59,122,940 raw reads were obtained from the control group, and 58,385,094 reads from the Vibrio-infected group. Via de novo assembly by Trinity assembler, 59,050 control unigenes and 73,946 Vibrio-infected group unigenes were obtained. By clustering unigenes from both libraries, a total of 64,411 standard unigenes were produced. The standard unigenes were annotated against the NCBI non-redundant, Swiss-Prot, Kyoto Encyclopaedia of Genes and Genome pathway (KEGG) and Orthologous Groups of Proteins (COG) databases, with 19,799 (30.73%), 16,832 (26.13%), 14,706 (22.83%) and 7,856 (12.19%) hits respectively, giving a final total of 22,455 significant hits (34.86% of all unigenes). A Gene Ontology (GO) analysis search using the Blast2GO program resulted in 6,007 unigenes (9.32%) being categorized into 55 functional groups. A differential gene expression analysis produced a total of 14,569 unigenes aberrantly expressed, with 11,446 unigenes significantly up-regulated and 3,103 unigenes significantly down-regulated. The differentially expressed immune genes fall under various processes of the animal immune system. Conclusion: This study provided an insight into the antibacterial mechanism in M. rosenbergii and the role of differentially expressed immune genes in response to V. parahaemolyticus infection. Furthermore, this study has generated an abundant list of transcript from M.rosenbergii which will provide a fundamental basis for future genomics research in this field. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that electroacupuncture (EA) has a significant effect on acute pain, but it has not solved the clinical problem of the chronification of acute pain. Diffuse noxious inhibitory controls (DNIC) function as a reliable indicator to predict the risk of chronic pain events. DNIC function in knee osteoarthritis (KOA) patients has been demonstrated to gradually decrease during the development of chronic pain. The purpose of this study is to conduct a randomized, controlled clinical trial to determine if EA can repair impaired DNIC function and thus prevent chronification of the acute pain of KOA. Methods/Design: This is a multicenter, single blind, randomized, controlled, three-arm, large-scale clinical trial. A total of 450 KOA patients will be randomly assigned to three groups. The strong EA group will receive EA with high-intensity current (2 mA < current < 5 mA) at the ipsilateral 'Neixiyan' (EX-LE5), 'Dubi'(ST35), 'Liangqiu'(ST34) and 'Xuehai' (SP10). The weak EA group will receive EA with low-intensity current (0 mA < current < 0.5 mA) on the same acupoints. The sham EA group will receive EA with low-intensity current (0 mA < current < 0.5 mA) with fine needles inserted superficially into the sites 2 cm lateral to the above acupoints. The patients will be treated with EA once a day, 30 minutes per session, in 5 sessions per week, for 2 weeks. In order to determine the best stage of KOA for effective EA intervention, patients within the treatment groups also will be divided into four stages. The primary outcomes are Visual Analog Scale (VAS), DNIC function and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Clinical assessments will be evaluated at baseline (before treatment) and after 5 to 10 sessions of treatment. Discussion: This trial will be helpful in identifying whether strong EA is more effective than weak EA in reversing chronification of acute pain through repairing the impaired DNIC function and in screening for the best stage of KOA for effective EA intervention. [ABSTRACT FROM AUTHOR]

Background: Immunohistochemistry (IHC) for napsin A has been widely used to support a diagnosis of lung adenocarcinoma with high sensitivity. In this study, we evaluated immunoreactivity for napsin A in a broad spectrum of renal neoplasms by using tissue microarrays (TMA). Methods: Duplicate TMA of 159 surgically excised renal neoplasms of various types were constructed. IHC for napsin A was performed on TMAs with appropriate positive and negative controls. Results: Napsin A was expressed in Acquired cystic disease associated renal cell carcinoma (RCC) (2/2, 100.0%), chromophobe RCC (5/45, 11.1%), clear cell RCC (10/23, 43.5%), clear cell papillary RCC (9/19, 47.4%), metanephric adenoma (3/3, 100.0%), oncocytoma (13/23, 56.5%), and papillary RCC (31/37, 83.8%). Expression of napsin A was not seen in mucinous tubular and spindle cell carcinoma (0/1, 0.0%), TFE/MITF RCC 0/1, 0.0%), and urothelial carcinoma (0/6, 0.0%). Conclusions: Napsin A is expressed in both common and rare sub-types of renal neoplasms with variable sensitivity. Based on our results, napsin A is not specific for lung adenocarcinoma. When a metastatic carcinoma of unknown primary is positive for napsin A, the differential diagnosis should include tumors of both renal and lung origin. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx. eu/vs/9558727831304717. [ABSTRACT FROM AUTHOR]

Background Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure. Methods In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc). Results 100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients receiving taVNS significantly differed in measures of FPG (F(2) = 10.62, p < 0.001), 2hPG F(2) = 25.18, p < 0.001) and HbAlc (F(1) = 12.79, p = 0.001) over the course of the 12 week treatment period. Conclusions Our study suggests that taVNS is a promising, simple, and cost-effective treatment for IGT/ pre-diabetes with only slight risk of mild side-effects. [ABSTRACT FROM AUTHOR]

Background Functional constipation (FC) is highly prevalent in the general population of the world and has a substantial negative impact on the health-related quality of life of individuals. Many clinical trials have indicated that acupuncture is effective in the treatment of FC. However, the sample sizes of these previous studies were too small. Furthermore, there are no reports investigating the relationship between the stimulation parameter and the therapeutic effect. We therefore designed a multicenter randomized controlled trial to address these problems and hopefully provide a more conclusive answer to these questions. Methods Participants will be included if they meet all of the following conditions: (1) diagnosed with functional constipation according to the Roman III standard; (2) aged between 18 and 65 years; (3) not taking any drugs that promote gastrointestinal movements at least during the 1 week prior to randomization; (3) willing to sign an informed consent form; (4) willing to return to the study site for their study visits. The participants will be randomly assigned to three groups in a 1:1:1 ratio: high current intensity group, low current intensity group, and mosapride citrate control group. The total study period is 9 weeks for each patient, 1 week for baseline, 4 weeks for treatment, and 4 weeks for follow-up. The primary outcome in this trial is the number of defecating events per week. The secondary outcomes will include the shape and properties of the stool, intensity of defecating difficulty, Patient Assessment of Constipation Quality of Life (PAC-QOL), MOS item Short Form health survey (SF-36), Self- Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Discussion This study will provide significant evidence for the application of acupuncture in FC and will identify a suitable stimulation parameter for treatment. [ABSTRACT FROM AUTHOR]

Background: The afferent projections from the auricular branch of the vagus nerve (ABVN) to the nucleus tractus solitaries (NTS) have been proposed as the anatomical basis for the increased parasympathetic tone seen in auriculo-vagal reflexes. As the afferent center of the vagus nerve, the NTS has been considered to play roles in the anticonvulsant effect of cervical vagus nerve stimulation (VNS). Here we proposed an "auriculo-vagal afferent pathway" (AVAP), by which transcutaneous auricular vagus nerve stimulation (ta-VNS) suppresses pentylenetetrazol (PTZ)-induced epileptic seizures by activating the NTS neurons in rats. Results: The afferent projections from the ABVN to the NTS were firstly observed in rats. ta-VNS increased the first grand mal latency of the epileptic seizure and decreased the seizure scores in awake rats. Furthermore, when the firing rates of the NTS neurons decreased, epileptiform activity manifested as electroencephalogram (EEG) synchronization increased with 0.37±0.12 s delay in anaesthetized rats. The change of instantaneous frequency, mean frequency of the NTS neurons was negative correlated with the amplitude of the epileptic activity in EEG traces. ta-VNS significantly suppressed epileptiform activity in EEG traces via increasing the firing rates of the neurons of the NTS. In comparison with tan-VNS, the anticonvulsant durations of VNS and ta-VNS were significantly longer (P<0.01). There was no significant difference between the anticonvulsant durations of VNS and ta-VNS (P>0.05). The anticonvulsant effect of ta-VNS was weakened by reversible cold block of the NTS. Conclusions: There existed an anatomical relationship between the ABVN and the NTS, which strongly supports the concept that ta-VNS has the potential for suppressing epileptiform activity via the AVAP in rats. ta-VNS will provide alternative treatments for neurological disorders, which can avoid the disadvantage of VNS. [ABSTRACT FROM AUTHOR]

Background: Community-based programs are being widely adopted in the struggle to prevent cardiovascular diseases. No study has been conducted in Japan to evaluate the effects of a community-based health promotion program by using the Framingham risk score and 10-year CHD risk as outcome variables. The aim of the present study was to assess the effects of a program involving 6-month intervention and 18-month follow-up using such outcomes. Methods: Participants (n = 1,983, 39.5% women, mean age 63.4 years) were selected for the study in 2008. Of these 1,983, 347 (42.4% women) subjects received the 6-month intervention. The intervention included individual counseling and group sessions, among others. After 18 months, 1,278 participants (intervention group: 238, control group: 1,040) were followed up. Changes in the Framingham risk score and 10-year coronary heart disease (CHD) risk were evaluated. ANCOVA and multiple logistic models adjusted for baseline value, age, sex and intervention times were used. Results: The results showed that the differences in the Framingham risk score and mean 10-year CHD risk were significant in the intervention group compared with the control group after 6-month follow-up (-0.46 and -1.12, respectively) and were also significant after 18-month follow-up (-0.39 and -0.85, respectively). The proportion of those with intermediate 10-year CHD risk (> = 10%) was significantly lower at 6 months (OR 0.30, 95% CI 0.12-0.74) and at 18 months (OR 0.41, 95% CI 0.19-0.92). Conclusions: The six-month intervention program effectively decreased estimated 10-year CHD risk and the effects were still present at 18-month follow-up. [ABSTRACT FROM AUTHOR]

Follicular thyroid carcinoma (FTC) tends to metastasize to remote organs rather than local lymph nodes. Separation of FTC from follicular thyroid adenoma (FTA) relies on detection of vascular and/or capsular invasion. We investigated which vascular markers, CD31, CD34 and D2-40 (lymphatic vessel marker), can best evaluate vascular invasion and why FTC tends to metastasize via blood stream to remote organs. Thirty two FTCs and 34 FTAs were retrieved for evaluation. The average age of patients with FTA was 8 years younger than FTC (p = 0.02). The female to male ratio for follicular neoplasm was 25:8. The average size of FTC was larger than FTA (p = 0.003). Fourteen of 32 (44%) FTCs showed venous invasion and none showed lymphatic invasion, with positive CD31 and CD34 staining and negative D2-40 staining of the involved vessels. The average number of involved vessels was 0.88 ± 1.29 with a range from 0 to 5, and the average diameter of involved vessels was 0.068 ± 0.027 mm. None of the 34 FTAs showed vascular invasion. CD31 staining demonstrated more specific staining of vascular endothelial cells than CD34, with less background staining. We recommended using CD31 rather than CD34 and/or D2-40 in confirming/ excluding vascular invasion in difficult cases. All identified FTCs with vascular invasions showed involvement of venous channels, rather than lymphatic spaces, suggesting that FTCs prefer to metastasize via veins to distant organs, instead of lymphatic vessels to local lymph nodes, which correlates with previous clinical observations. [ABSTRACT FROM AUTHOR]