Identification of immune-related genes and development of a prognostic model in mantle cell lymphoma.

Background: The immune landscape, prognostic model, and molecular variations of mantle cell lymphoma (MCL) remain unclear. Hence, an integrated bioinformatics analysis of MCL datasets is required for the development of immunotherapy and the optimization of targeted therapies. Methods: Data were obtained from the Gene Expression Omnibus (GEO) database (GSE32018, GSE45717 and GSE93291). The differentially expressed immune-related genes were selected, and the hub genes were screened by three machine learning algorithms, followed by enrichment and correlation analyses. Next, MCL molecular clusters based on the hub genes were identified by K-Means clustering, the probably approximately correct (PAC) algorithm, and principal component analysis (PCA). The landscape of immune cell infiltration and immune checkpoint molecules in distinct clusters was explored by single-sample gene-set enrichment analysis (ssGSEA) as well as the CIBERSORT and xCell algorithms. The prognostic genes and prognostic risk score model for MCL clusters were identified by least absolute shrinkage and selection operator (LASSO)-Cox analysis and cross-validation for lambda. Correlation analysis was performed to explore the correlation between the screened prognostic genes and immune cells or immune checkpoint molecules. Results: Four immune-related hub genes (CD247, CD3E, CD4, and GATA3) were screened in MCL, mainly enriched in the T-cell receptor signaling pathway. Based on the hub genes, two MCL molecular clusters were recognized. The cluster 2 group had a significantly worse overall survival (OS), with down-regulated hub genes, and a variety of activated immune effector cells declined. The majority of immune checkpoint molecules had also decreased. An efficient prognostic model was established, including six prognostic genes (LGALS2, LAMP3, ICOS, FCAMR, IGFBP4, and C1QA) differentially expressed between two MCL clusters. Patients with a higher risk score in the prognostic model had a poor prognosis. Furthermore, most types of immune cells and a range of immune checkpoint molecules were positively correlated with the prognostic genes. Conclusions: Our study identified distinct molecular clusters based on the immune-related hub genes, and showed that the prognostic model affected the prognosis of MCL patients. These hub genes, modulated immune cells, and immune checkpoint molecules might be involved in oncogenesis and could be potential prognostic biomarkers in MCL.

Compelling Evidence Linking CD40 Gene With Graves' Disease in the Chinese Han Population.

Mutations in CD40 have been widely reported to be risk factors for Graves' disease (GD). The gene, along with its cognate ligand CD40L, may regulate pro-inflammatory and immune responses. Rs1883832, located at the -1 position of the Kozak sequence, is the most well-studied single nucleotide polymorphism (SNP) of CD40, and has been confirmed to predispose those with the alteration to GD, regardless of ethnicity. Our genome-wide association study (GWAS) indicated that several SNPs, including rs1883832 located within the vicinity of CD40 were associated with GD in the Han Chinese population. Aiming at identifying the most consequential SNP and its underlying pathogenic mechanism, we performed a two-stage refined study on 8,171 patients with GD and 7,906 controls, and found rs1883832 was the most significantly GD-associated SNP in the CD40 gene region (PCombined = 9.17×10-11, OR = 1.18). Through searching the cis-expression quantitative trait locus database and using quantitative RT-PCR, we further discovered that the rs1883832 genotype can influence CD40 gene transcription. Furthermore, we demonstrated that rs1883832 is a susceptibility locus for pTRAb+ GD patients. In conclusion, the current study provides robust evidence that rs1883832 can regulate CD40 gene expression and affect serum TRAb levels, which ultimately contributes to the development of GD.

Penfluridol triggers mitochondrial-mediated apoptosis and suppresses glycolysis in colorectal cancer cells through down-regulating hexokinase-2.

Penfluridol, a commonly used antipsychotic agent in a clinical setting, exhibits potential anticancer properties against various human malignancies. Here, we investigated the effect of penfluridol on the biological behavior of colorectal cancer (CRC) cells. Cell viability and clonogenic potential were detected by the cell counting kit-8 and colony formation assay. The cell apoptosis and cell cycle distribution were quantified through flow cytometry. Caspase-3 activity, glucose consumption, lactate production, and intracellular ATP levels were evaluated using the corresponding commercial detection kits. The protein levels of related genes were detected through western blotting. Mitochondrial membrane potential was detected using JC-1 staining. A CRC xenograft tumor model was used to validate the antitumor activity of penfluridol in vivo. Penfluridol reduced cell survival and promoted apoptotic cell death effectively through the mitochondria-mediated intrinsic pathway in a dose-dependent manner. Furthermore, the process of glycolysis in HCT-116 and HT-29 cells was inhibited upon penfluridol treatment, as evidenced by the decrease in glucose consumption, lactate production, and intracellular ATP levels. Further mechanistic studies revealed that penfluridol influenced cell apoptosis and glycolysis in CRC cells by downregulating hexokinase-2 (HK-2). The proapoptotic effect and glycolytic inhibition-induced by penfluridol were effectively reversed by HK-2 overexpression. Consistent with in vitro results, penfluridol could also suppress tumor growth and trigger apoptosis in vivo. Penfluridol triggers mitochondrial-mediated apoptosis and induces glycolysis inhibition via modulating HK-2 in CRC and provides a theoretical basis to support penfluridol as a repurposed drug for CRC patients.

[Acupuncture ameliorates negative emotion in PCOS patients: a randomized controlled trial].

OBJECTIVE: To evaluate the effectiveness and possible mechanism of acupuncture treatment for negative emotion in patients with polycystic ovary syndrome (PCOS). METHODS: A total of 40 PCOS patients were randomly divided into an observation group and a control group, 20 cases in each one. Both groups received lifestyle interventions (exercise and diet guidance) on the 5th day of menstruation. On the basis of above treatment, the patients in the observation group received acupuncture at Guanyuan (CV 4), Zhongwan (CV 12), Guilai (ST 29), Futu (ST 32), Liangqiu (ST 34), Sanyinjiao (SP 6), Zusanli (ST 36), Hegu (LI 4), Shenmen (HT 7), Baihui (GV 20) as the main acupoints, and connected the electroacupuncture (continuous wave, 2 Hz, 30 min), once every other day, 3 times a week. The treatment for 1 month was as one course and 4 courses were required totally in both groups. Before and after treatment, the body mass index (BMI), ferriman-gallway (F-G) score, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score, PCOS health-related quality of life questionnaire (PCOSQ) score were observed, meanwhile, serum sex hormone, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progestin (P), prolactin (PRL), testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) levels, and serumß-endorphin levels were detected. RESULTS: Compared with before treatment, the BMI, F-G score, SAS score, SDS score and serum FAI level were decreased and the PCOSQ score and the levels of serum SHBG andß-endorphin were increased in the observation group after treatment (all P<0.05). Compared with before treatment, the SDS score was decreased in the control group after treatment (P<0.05). Compared with the control group, the F-G score, SDS score, SAS score, and serum FAI level were lower, and the PCOSQ score and serumß-endorphin level were higher in the observation group after treatment (all P<0.05). CONCLUSION: Applying acupuncture to the treatment of patients with PCOS can effectively relieve anxiety and depression, and the mechanism may be related to the regulation on the levels of serumß-endorphin and androgen.

Polyoxometalate-Based Metal-Organic Frameworks with Conductive Polypyrrole for Supercapacitors.

Metal-organic frameworks (MOFs) with high porosity could act as an ideal substitute for supercapacitors, but their poor electrical conductivities limit their electrochemical performances. In order to overcome this problem, conductive polypyrrole (PPy) has been introduced and a novel nanocomposite resulting from polyoxometalate (POM)-based MOFs (NENU-5) and PPy has been reported. It comprises the merits of POMs, MOFs, and PPy. Finally, the highly conductive PPy covering the surfaces of NENU-5 nanocrystallines can effectively improve the electron/ion transfer among NENU-5 nanocrystallines. The optimized NENU-5/PPy nanocomposite (the volume of Py is 0.15 mL) exhibits high specific capacitance (5147 mF·cm-2), larger than that of pristine NENU-5 (432 mF·cm-2). Furthermore, a symmetric supercapacitor device based on a NENU-5/PPy-0.15 nanocomposite possesses an excellent areal capacitance of 1879 mF·cm-2, which is far above other MOF-based supercapacitors.

Upregulation of miR-216a exerts neuroprotective effects against ischemic injury through negatively regulating JAK2/STAT3-involved apoptosis and inflammatory pathways.

OBJECTIVE: Ischemic stroke remains a significant cause of death and disability in industrialized nations. Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) of the JAK2/STAT3 pathway play important roles in the downstream signal pathway regulation of ischemic stroke-related inflammatory neuronal damage. Recently, microRNAs (miRNAs) have emerged as major regulators in cerebral ischemic injury; therefore, the authors aimed to investigate the underlying molecular mechanism between miRNAs and ischemic stroke, which may provide potential therapeutic targets for ischemic stroke. METHODS: The JAK2- and JAK3-related miRNA (miR-135, miR-216a, and miR-433) expression levels were detected by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis in both oxygen-glucose deprivation (OGD)-treated primary cultured neuronal cells and mouse brain with middle cerebral artery occlusion (MCAO)-induced ischemic stroke. The miR-135, miR-216a, and miR-433 were determined by bioinformatics analysis that may target JAK2, and miR-216a was further confirmed by 3' untranslated region (3'UTR) dual-luciferase assay. The study further detected cell apoptosis, the level of lactate dehydrogenase, and inflammatory mediators (inducible nitric oxide synthase [iNOS], matrix metalloproteinase-9 [MMP-9], tumor necrosis factor-α [TNF-α], and interleukin-1ß [IL-1ß]) after cells were transfected with miR-NC (miRNA negative control) or miR-216a mimics and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) damage with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V-FITC/PI, Western blots, and enzyme-linked immunosorbent assay detection. Furthermore, neurological deficit detection and neurological behavior grading were performed to determine the infarction area and neurological deficits. RESULTS: JAK2 showed its highest level while miR-216a showed its lowest level at day 1 after ischemic reperfusion. However, miR-135 and miR-433 had no obvious change during the process. The luciferase assay data further confirmed that miR-216a can directly target the 3'UTR of JAK2, and overexpression of miR-216a repressed JAK2 protein levels in OGD/R-treated neuronal cells as well as in the MCAO model ischemic region. In addition, overexpression of miR-216a mitigated cell apoptosis both in vitro and in vivo, which was consistent with the effect of knockdown of JAK2. Furthermore, the study found that miR-216a obviously inhibited the inflammatory mediators after OGD/R, including inflammatory enzymes (iNOS and MMP-9) and cytokines (TNF-α and IL-1ß). Upregulating miR-216a levels reduced ischemic infarction and improved neurological deficit. CONCLUSIONS: These findings suggest that upregulation of miR-216a, which targets JAK2, could induce neuroprotection against ischemic injury in vitro and in vivo, which provides a potential therapeutic target for ischemic stroke.

Multiregion sequencing reveals the intratumor heterogeneity of driver mutations in TP53-driven non-small cell lung cancer.

Intratumor heterogeneity (ITH) in non-small cell lung cancer (NSCLC) may account for resistance after a period of targeted therapies because drugs destroy only a portion of tumor cells. The recognition of ITH helps identify high-risk patients to make effective treatment decisions. However, ITH studies are confounded by interpatient heterogeneity in NSCLC and a large amount of passenger mutations. To address these issues, we recruited NSCLC patients carrying TP53 mutations and selected driver mutations within recurrently mutated genes in NSCLC. A total of 12-paired normal-tumor tissues were subjected to whole-genome/whole-exome sequencing. From these, 367 non-silent mutations were selected as driver mutations and deeply sequenced in 61 intratumoral microdissections. We identified a universal prevalence of heterogeneity in all 12 tumors, indicating branched evolution. Although TP53 mutations were observed in single biopsy of all 12 tumors, most tumors consist of both TP53 mutated and non-mutated cells in separate regions within the same tumor. This suggests the late molecular timing of the acquisition of TP53 mutations; therefore, the detection of TP53 mutations in a single biopsy may simply not reflect the early malignant potential. In addition, we identified regions of loss of heterozygosity surrounding TP53 and CDKN2A mutations in tumor 711, which also exhibited heterogeneity in different regional samples. Because the ITH of driver mutations likely has clinical consequences, further efforts are needed to limit the impact of ITH and to improve therapeutic efficiency, which will benefit NSCLC patients receiving targeted treatments.

Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations.

Thyroid-stimulating hormone (TSH) is a sensitive indicator of thyroid function. High and low TSH levels reflect hypothyroidism and hyperthyroidism, respectively. Even within the normal range, small differences in TSH levels, on the order of 0.5-1.0 mU/l, are associated with significant differences in blood pressure, BMI, dyslipidemia, risk of atrial fibrillation and atherosclerosis. Most of the variance in TSH levels is thought to be genetically influenced. We conducted a genome-wide association study of TSH levels in 1346 Chinese Han individuals. In the replication study, we genotyped four candidate SNPs with the top association signals in an independent isolated Chinese She cohort (n = 3235). We identified a novel serum TSH susceptibility locus within XKR4 at 8q12.1 (rs2622590, Pcombined = 2.21 × 10(-10)), and we confirmed two previously reported TSH susceptibility loci near FOXE1 at 9q22.33 and near CAPZB at 1p36.13, respectively. The rs2622590_T allele at XKR4 and the rs925489_C allele near FOXE1 were correlated with low TSH levels and were found to be nominally associated to patients with papillary thyroid carcinoma (PTC) (OR = 1.41, P= 0.014 for rs2622590_T, and OR = 1.61, P= 0.030 for rs925489_C). The rs2622590 and rs925489 genotypes were also correlated with the expression levels of FOXE1 and XKR4, respectively, in PTC tissues (P = 2.41 × 10(-4) and P= 0.02). Our findings suggest that the SNPs in XKR4 and near FOXE1 are involved in the regulation of TSH levels.

Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis.

Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.

[Serum level of programmed cell death 5 protein levels in patients with sepsis].

OBJECTIVE: To investigate the changes of serum programmed cell death 5 (PDCD5) levels in patients with critical illnesses including systemic inflammatory response syndrome (SIRS, except sepsis), sepsis (except severe sepsis) and severe sepsis. METHODS: A total of 78 patients were enrolled in this study, of whom, 28 were with SIRS, 23 with sepsis and 27 with severe sepsis. Twenty-two healthy individuals were included as controls. The levels of serum PDCD5 were evaluated by enzyme-linked immune sorbent assay. And the correlation analyses were made in the levels of sreum PDCD5 and acute physiology and chronic health evaluation II(APACHE II), high-sensitivity C-reactive protein(hs-CRP), white blood cell count, neutrophil count and age factors. RESULTS: Serum PDCD5 levels in the SIRS, sepsis and severe sepsis groups were (19.07 ± 8.91), (29.03 ± 13.27) and (42.83 ± 17.32) µg/L respectively, which were significantly higher than that in the healthy control group (0.32 ± 0.02) µg/L. Serum PDCD5 levels in SIRS, sepsis and severe sepsis groups were gradually increased with significant difference at any in-between comparison (P<0.05). Moreover, serum PDCD5 levels were positively correlated with the acute physiology and chronic health evaluation II (APACHE II) score (r=0.572, P<0.05). CONCLUSION: The serum PDCD5 levels in the critically ill patients with sepsis were progressively increased with the worsened condition. The up-regulated expression of PDCD5 may play an important role in the development and progression of sepsis.

[Evaluation of X-ray beam angulation for successful four canals identification in the mandibular first molars].

PURPOSE: This study was aimed to determine the most effective horizontal beam angulation to identify 4 canals in the mandibular first molars, so as to provide full and accurate information for the clinic. METHODS: One hundred and twenty mandibular first molars with four canals that needed endodontic treatment in vivo were selected. Radiographs were taken at horizontal angles of 0,10,20 degrees from distal direction and 0,10,20,30 degrees from mesial direction of the tooth. The numbers of root canal and the degree of resolution were identified and recorded by 3 independent observers. Data were analyzed using SPSS10.0 software package or Chi-square test. RESULTS: At 30 and 20 degrees from mesial direction, 93.3% and 90.0% of all the 120 teeth were correctly identified as 4 canals, compared with 0 degree of 40.0%(P<0.01). Of them, 71.5% and 89.7% could be classified as with high resolution, respectively. The latter was not significantly lower than 0 degree of 95.0% (P>0.05). CONCLUSION: Twenty degrees from mesial direction is the most effective X-ray beam angle in diagnosing 4 canals of the first mandibular molars. Supported by Research Fund of Science and Technology Commission of Shanghai Municipality (Grant No.08DZ2271100).

Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro.

AIM: To examine the inhibitory effects of adenosine monophosphate-activated protein kinase (AMPK) activation on cardiac hypertrophy in vitro and to investigate the underlying molecular mechanisms. METHODS: Cultured neonatal rat cardiomyocytes were treated with the specific AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the specific AMPK antagonist Compound C, and then stimulated with phenylephrine (PE). The Muscle RING finger 1 (MuRF1)-small interfering RNA (siRNA) was transfected into cardiomyocytes using Lipofectamine 2000. The surface area of cultured cardiomyocytes was measured using planimetry. The protein degradation was determined using high performance liquid chromatography (HPLC). The expression of beta-myosin heavy chain (beta-MHC) and MuRF1, as well as the phosphorylation levels of AMPK and Forkhead box O 1 (FOXO1), were separately measured using Western blot or real-time polymerase chain reaction. RESULTS: Activation of AMPK by AICAR 0.5 mmol/L inhibited PE-induced increase in cardiomyocyte area and beta-MHC protein expression and PE-induced decrease in protein degradation. Furthermore, AMPK activation increased the activity of transcription factor FOXO1 and up-regulated downstream atrogene MuRF1 mRNA and protein expression. Treatment of hypertrophied cardiomyocytes with Compound C 1 micromol/L blunted the effects of AMPK on cardiomyocyte hypertrophy and changes to the FOXO1/MuRF1 pathway. The effects of AICAR on cardiomyocyte hypertrophy were also blocked after MuRF1 was silenced by transfection of cardiomyocytes with MuRF1-siRNA. CONCLUSION: The present study demonstrates that AMPK activation attenuates cardiomyocyte hypertrophy by modulating the atrophy-related FOXO1/MuRF1 signaling pathway in vitro.

[Clinical effect of three kinds of rotary nickel-titanium instruments on root canal preparation of molars].

PURPOSE: To evaluate three kinds of nickel-titanium instruments applied to molar root canal preparation. METHODS: A total of 90 molars treated by root canal therapy were randomly assigned to three groups: ProTaper group. K3 group and Mtwo group. Crown-down technique was used in ProTaper and K3 group, while Mtwo group was treated with routine preparation technique. All teeth in 3 groups were filled by lateral condensation technique. Treatment effect of 3 groups was evaluated according to pre- and post-operative X-ray films. Wearing and tearing degree of equipment, preparation time and postoperative complications incidence of 3 groups were also compared. All statistical analysis was performed using SAS9.0 software package. Data of root canal curvatures and preparation time was compared using t test; the incidence of complications of root canal treatment and postoperative pain was analyzed using Chi-square test. RESULTS: In three groups, root canals had no deviation or no ledge, could maintain the root canal anatomy in early form, and achieved good preparation results. In this study, four ProTapers, three K3s and one Mtwo instrument were fractured. The average root canal preparation time of the Mtwo group was 3.94 min, significantly less than the ProTaper (4.71 min) group and the K3(4.58 min) group. CONCLUSIONS: Three rotary nickel-titanium systems tested in this study are effective in the molar root canal preparation. The Mtwo instrument is much easier and faster during preparation with routine preparation technique.Supported by Research Fund of Science and Technology Commission of Shanghai Municipality(Grant No.08DZ2271100).

[Thyrocytes contribute to their own demise: the role of interleukin-18 in Hashimoto's thyroiditis].

OBJECTIVE: To investigate the IL-18 expression in the thyroid tissues of Hashimoto's thyroiditis (HT) and its cellular localization and the effect of interferon-gamma (IFN-gamma) on the interleukin- (IL)-18 expression in thyrocytes. METHODS: RT-PCR and immunohistochemistry were used to detect the IL-18 expression and its cellular localization in the thyroid tissues biopsy specimens of 6 HT patients with normal thyroid function, 6 normal thyroid specimens resected from patients with pharyngeal carcinoma, and 16 specimens of thyroid tissues adjacent to the thyroid adenoma obtained during operation. Thyrocytes were isolated, cultured, and exposed to IL-1beta, tumor necrosis factor-alpha (TNF-alpha), or IFN-gamma for 48 h. RT-PCR and Western blotting were used to detect the IL-18 expression. RESULTS: IL-18 mRNA expression was at an extremely low levels in the normal thyroid tissues and at a significantly higher level in the thyroid tissues of HT. Immunohistochemical staining showed that IL-18 expression was augmented in the thyroid tissues of HT and was mainly localized in the thyroid follicular cells. The IL-18 mRNA expression in the isolated human thyrocytes was dose-dependently elevated by IFN-gamma rather than TNF-alpha or IL-1beta. Western blotting showed that pro-IL-18, but not mature IL-18, was detected in the lysates of the cultured human thyrocytes and the expression of pro-IL-18 was increased by IFN-gamma. CONCLUSION: IL-18 expression is elevated in the thyroid follicular cells of HT. IL-18 is constitutively expressed in the isolated human thyrocytes and its expression is up-regulated by IFN-gamma. Therefore, interplay between IL-18 and IFN-gamma may have an important role in the thyrocytes destruction in HT.

[Diagnosis and treatment of 17 alpha-hydroxylase deficiency: a case report and literature review].

A 16-year-old "female" patient presented as hypertension, hypokalemia, male pseudohermaphroditism, lowered gonadal steroids and cortisol, elevated adrenocorticotropic hormone and pituitary gonadotropin, and 46 XY karyotype. The patient was diagnosed as 17 alpha-hydroxylase deficiency, a rare case of congenital adrenal hyperplasia. "She" chose to remain female appearance and social gender after negotiation with the parents. Cryptor-chidism of both inguinal canals was surgically removed for preventing canceration. After the surgery, a very small daily dose of dexamethasone (0.187 5 mg at bedtime) was enough to control hypertension and hypokalemia, and the therapy of conjugated estrogens (Premarin) was given to promote the development of female characters. After 6 months of treatment, normotension and normokalemia remained, and pubarche and mammogenesis emerged.

[Ghrelin expression in the tissues of different thyroid diseases].

OBJECTIVE: To investigate whether ghrelin, a novel endogenous ligand of growth hormone secretagogue receptor (GHS-R), was expressed in the thyroid tissues of different thyroid diseases, and its implication. METHODS: The paraffin-embedded specimens of thyroid tissues from 2000 to 2004 were obtained from 57 patients with different thyroid diseases, including 5 subacute thyroiditis, 8 Hashimoto's thyroiditis, 7 hyperthyroidism (Graves disease), 8 nodular goiter, 5 thyroid adenoma, 3 thyroid lymphoma, 8 papillary carcinoma, 3 follicular carcinoma, 5 medullary carcinoma and 5 undifferentiated carcinoma cases. The specimens of normal peri-adenoma thyroid tissues served as controls. Immunohistochemical staining was used to detect ghrelin expression. RESULTS: (1) ghrelin expression was undetectable in the thyroid tissues of normal control, subacute thyroiditis, Hashimoto's thyroiditis and Graves disease. (2) ghrelin expression was also undetected in the tissues of nodular goiter, thyroid adenoma and thyroid lymphoma. (3) ghrelin-positive staining was found in the tumor cells of different types of thyroid carcinoma. Five cases were positive within 8 cases in papillary carcinoma, 2 cases were positive within 3 cases in follicular carcinoma, 3 cases were positive within 5 cases in medullary carcinoma, 3 cases were positive within 5 cases in undifferentiated carcinoma. CONCLUSION: Ghrelin is expressed in malignant epithelial thyroid neoplasms, but not in autoimmune or inflammatory thyroid diseases and benign nodular thyroid diseases. The results indicate that ghrelin expression may play an important role in the occurrence and development of thyroid carcinoma.