Objective To study the expression of mitochondrial tumor suppressor gene 1 (MTUS1) mR-NA in papillary thyroid carcinoma(PTC).Methods Reverse transcription polymerase chain reaction(RT-PCR) was used to detect MTUS1 mRNA level in 68 cases of human PTC and the adjacent non-cancerous epithelium (NCE) specimens.Results The relative expression value of MTUS1 mRNA in PTC was 0.31 ± 0.09,while it was 0.65 ±0.12 in NCE.The difference had statistical significance between the 2 groups(t =2.39,P ＜0.05).In PTC,mRNA expression of MTUS1 gene was related to the pathological grade,and lymph node metastasis(P ＜ 0.05)while it was not related to patients' age,sex,differentiation degree,tumor size or TNM stage(P ＞ 0.05).Conclusion mRNA expression of MTUS1 gene is lower in PTC than in NCE,which may play an important role in carcinogenesis and progression of PTC.

Objective Methylation of anti-oncogene can be demethylated by related drugs which can help the inactivated gene to express again .This study aims to study the effects of the demethylating agent 5-Aza-2′-deoxycytidine on the growth of human thyroid papillary cancer cell line TPC-1 and mRNA and protein expres-sion of KLF4.Methods TPC-1 cells were treated with different concentration of 5-Aza-CdR.MTT was used to detect the influence of 5-Aza-CdR on cell proliferation .RT-PCR was used to detect mRNA and protein expression levels of KLF4.Results After being treated with 5-Aza-CdR for 24 hours, 48 hours, and 72 hours, the growth of TPC-1 cells was inhibited and the inhibition was in time and concentration depended manner .After treatment with 5-Aza-CdR, mRNA and protein expression levels of KLF 4 were increased, and the difference had statistical significance(P<0.05).Conclusion 5-Aza-CdR can inhibit the cell viability of TPC-1 cells through upregulat-ing KLF4 expression , which may provide experimental basis for 5-Aza-CdR in treating thyroid cancer .

OBJECTIVETo study the clinicopathologic features and diagnosis of intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

METHODSNineteen cases of IPMN encountered during the period from 1999 to 2007 were studied by light microscopy and immunohistochemistry.

RESULTSIPMN occurred more often in males (68%). It affected patients in older age group (mean age = 59) and was located mainly in the head of pancreas (60%). The mean tumor size was 4.2 cm (range = 1 to 8 cm). The clinical presentation was epigastric pain (53%), weight loss (32%), diabetes (21%), pancreatitis (21%) and jaundice (10%). Pancreatectomy was performed in 18 cases. The remaining patient received bypass surgery only. Features of in-situ or invasive malignancy were present in 15 of the 19 cases (78%). Histologically, the tumor consisted of papillary proliferations protruding into and expanding the pancreatic ducts. Invasion into the surrounding pancreatic parenchyma was noted in 12 cases and chronic pancreatitis was present in 16 cases. Follow-up data (4 to 48 months) were available in 13 patients. Apart from 1 patient who died of other disease, all were still alive. Immunohistochemical study showed that p53 was positive in 6 cases, p16 in 5 cases and fascin in 8 cases. The expression of c-erbB-2 was all negative. Ki-67 index ranged from 1% to 80% (mean = 38%).

CONCLUSIONSMalignant changes are not uncommon in IPMN. The prognosis after surgical resection however is better than that of conventional pancreatic adenocarcinoma. The overexpression of p53, p16 and fascin may be related to tumor progression. The possibility of malignant transformation needs to be considered if the Ki-67 index is over 15%. Early recognition by radiologic examination (including ERCP) and pancreatic cytology would be helpful in early diagnosis. Surgical resection represents the mainstay of treatment and long-term post-operative follow up is needed.

Adaptor Proteins, Signal Transducing ; analysis ; Adenocarcinoma, Mucinous ; diagnosis ; metabolism ; Adult ; Aged ; Carcinoma, Pancreatic Ductal ; diagnosis ; metabolism ; pathology ; Carcinoma, Papillary ; pathology ; Cell Cycle Proteins ; analysis ; Cholangiopancreatography, Endoscopic Retrograde ; Female ; Humans ; Immunohistochemistry ; trends ; Ki-67 Antigen ; analysis ; Male ; Middle Aged ; Pancreas ; metabolism ; pathology ; Pancreatectomy ; Pancreatic Ducts ; metabolism ; pathology ; Pancreatic Neoplasms ; diagnosis ; metabolism ; pathology ; Prognosis ; Receptor, ErbB-2 ; analysis ; Treatment Outcome

OBJECTIVETo investigate the protective effect of Yigan Fuzheng Paidu Capsules (YC) combined with medical ozone against hepatic injury in dogs induced by hepatotoxic drug.

METHODSTwenty-four dogs were randomized equally into 4 groups (n=6), namely the model group, oleanolic acid tablet (OAT) group, YC group and YC+O(3) group, given either no particular treatment, oral OAT at 10 mg/day, oral YC at 0.2 g/day, or YC at 0.2 g/day plus 150 ml medical ozone transrectal insufflation every other day, respectively, for totally 30 consecutive days. Acute hepatic injury was induced after the treatment in the dogs with a sing-dose intraperitoneal injection of 0.9 ml/kg CCl(4) and peanut oil mixture (1:1, W/W). The general condition, survival time, alanine aminotransferase (ALT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), serum total bilirubin (TBIL), prothrombin time (PT), blood ammonia (AMMO), and blood urea nitrogen (BUN) were recorded or measured. The hepatic pathological changes were observed upon death or on day 15 following CCl(4) injection.

RESULTSCompared with the other 3 treatment protocols, YC plus O(3) showed favorable effects on the activity, mental state, diet, urination and defecation of the dogs, which had significantly higher survival rate and higher levels of ALT, TBIL, PT, and AMMO than the model and OAT groups (P<0.05). AST/ALT remained normal in YC+O(3) group, which had also milder hepatic injury than the other 3 groups.

CONCLUSIONSYC combined with medical ozone may decrease transaminase and blood ammonia levels, relieve jaundice, prolong the survival time of dogs with CCl(4)-induced hepatic injury.

Alanine Transaminase ; blood ; Ammonia ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bilirubin ; blood ; Blood Urea Nitrogen ; Capsules ; Carbon Tetrachloride ; toxicity ; Dogs ; Drug Therapy, Combination ; Female ; Liver ; drug effects ; pathology ; Liver Diseases ; blood ; etiology ; prevention & control ; Male ; Medicine, Chinese Traditional ; Oxidants, Photochemical ; therapeutic use ; Ozone ; therapeutic use ; Survival Analysis

BACKGROUNDAtopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing.

METHODSHaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-γ (IFN-γ). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.

RESULTSIL-4/13 significantly reduced, while IFN-γ significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-γ significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-γ increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions.

CONCLUSIONSOur results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.

Caspase 14 ; metabolism ; Cell Line, Tumor ; Cells, Cultured ; Dermatitis, Atopic ; metabolism ; Humans ; Immunohistochemistry ; Interferon-gamma ; metabolism ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Intermediate Filament Proteins ; metabolism ; Keratinocytes ; enzymology ; metabolism ; Proteinase Inhibitory Proteins, Secretory ; metabolism ; Serine Peptidase Inhibitor Kazal-Type 5 ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

Objective: To evaluate anemia and related nutritional status of 6-17 years old boarding school students in rural areas of central and western China, and to reveal the difference of nutrition problems in different regions. Methods: In the central and western regions, Henan, Anhui, Jiangxi, Guangxi and Sichuan provinces, as well as Tibet Autonomous Region were selected for this survey considering similar per capita GDP levels. One secondary school and one primary school which participated in the National Nutrition Improvement Program for Rural Compulsory Education Students were selected from each province. One class was selected from each grade of every school by using cluster sampling method. A total of 2 180 students were selected in this survey. Venous blood was collected and the level of hemoglobin, ferritin, soluble transferrin receptor, folic acid and vitamin B12 was analyzed to evaluate anemia and nutrient deficiencies. Results: As for western region, prevalence of anemia among students aged 6-8 and 9-11 years was 3.2% and 2.9%, respectively; iron deficiency prevalence among students aged 6-8, 9-11 and 12-14 years was 10.8%, 13.8% and 24.3%, respectively; and folic deficiency prevalence among students aged 12-14 and 15-17 years was 32.7 % and 49.4%, respectively. Prevalence of anemia, iron and folic deficiency in those areas was significantly higher than those of central regions (all P <0.05). As for the central regions, vitamin B12 deficiency prevalence of students aged 6-8, 9-11, 12-14 and 15-17 years was 7.3%, 19.4%, 29.2% and 45.5% respectively, which was significantly higher than of those of the western regions at the same age group. Conclusion Anemia, iron deficiency and folic acid deficiency are more common among students in western region, while the vitamin B12 deficiency problem is more common in central region. There are regional differences in the nutritional problems of students in the rural areas of central and western part of China. Nutrition improvement of student needs to be adapted to local conditions.

Objective: To explore the relationship between one-child and low height level classification among children and adolescents, and the effects of fruits, vegetables and physical activities on this association, and to provide as cientific reference for probing into and improving the differences of their height level between one child and child with siblings. Methods: Using stratified cluster sampling method, 93 primary and secondary schools in 7 provinces and cities in China were selected for physical examination and questionnaire surveys. A total of 40 978 primary and middle school students aged 7-17 were selected. A multilevel Logistic regression model was used to analyze. Results: Univariate analysis found that being one-child was less likely to be classified as low height level(OR=0.63, 95%CI=0.58-0.67); the multilevel model also found that the probability that one-child being at low height level was still lower(OR=0.78, 95%CI=0.73-0.85), and daily vigorous-intensity physical activities ≥1 h (OR=0.92, 95%CI=0.85-0.99) and daily vegetables and fruits intake ≥5 servings (OR=0.83, 95%CI=0.75-0.92) could also reduce the probability of being at low height level. Hierarchical analysis found that when vegetables and fruits intake and physical activities time were sufficient, there was no longer a significant difference in the height level classification between one-child and child with siblings(P>0.05). Conclusion Being one-child could be a protective factor for the height level classification of children and adolescents. Adequate intake of vegetables and fruits and time of vigorous-intensity physical activities could fill the gap of height level classification between of being one-child and child with siblings. Effective behavioral intervention measures should be taken to protect the healthy growth of height among children and adolescences.

objective To evaluate the acute toxicity of recombinant trivalent human papillomavirus (HPV) vaccines.Methods Wistar rats were randomly divided into negative control and HPV groups with 20 rats in each group.Rats in HPV groups were sc administered with a single-dose of 1.5 mL of HPV vaccines (three times of human dose/each rat),while rats in negative control group were given equal volume of saline.The clinical state of animals was observed,and the body mass changes were detected.Rats were dissected after 15 d of treatment and examined by gross pathology.Results Following a single injection with high-dose HPV vaccines,there were not obvious abnormalities in clinical symptom.Compared with negative control group,the body weight of rats from HPV vaccines-treated group had no significant difference.No obvious macro-pathological change was found in all animals.Conclusion Single sc injection with recombinant trivalent HPV vaccines is well tolerated and no obvious toxicological change is found in Wistar rats.These results will facilitate further preclinical safety studies of HPV vaccines.

Long non-coding RNAs (LncRNAs) are abnormally expressed in a variety of tumors and participate in the occurrence and development of tumors. However, the expression and function of many LncRNAs in tumors have not been fully clarified. In this paper, 113 normal breast tissues and 1 109breast cancer tissues were analyzed in TCGT database. LncRNA AL133467. 1 was found to be lowly expressed in breast cancer tissues and negatively correlated with poor prognosis of breast cancer patients. The expression of AL133467. 1 in breast cancer cells was significantly lower than that in normal breast epithelial cells. We overexpressed AL133467. 1 in relatively low-expression breast cancer cells SKBR3and BT474, and cell count and plate colony-formation experiments showed that overexpression ofAL133467. 1 could significantly inhibit the proliferation and colony formation of breast cancer cells (P< 0. 01). Cell scratch and Transwell assays showed that the migration and invasion ability of breast cancer cells overexpressing AL133467. 1 was significantly reduced compared with the control group (P<0. 01). MiRDB database showed that AL133467. 1 had binding sites with miR-661. miR-661 could bind the transducer of ErbB2, 2 (ErbB2, 2, TOB2). qRT-PCR showed that miR-661 was highly expressed inbreast cancer cells and positively correlated with poor prognosis of breast cancer patients (P < 0. 001). Luciferase reporter assays showed that AL133467. 1 had specific binding to miR-661 (P < 0. 01). AL133467. 1 overexpression could inhibit the expression of miR-661 in breast cancer cells (P<0. 0001). Transfection of miR-661 mimics eliminated the inhibitory effect of overexpression of AL133467. 1 on breast cancer cells (P < 0. 001). In addition, qRT-PCR and Western blotting results showed that overexpression of AL133467. 1 up-regulated TOB2 mRNA (P < 0. 0001) and protein levels. But whenmiR-661 mimics were transfected, TOB2 mRNA (P < 0. 0001) and protein levels were significantly inhibited. In conclusion, as a competitive endogenous RNA of miR-661. AL133467. 1 promotes the expression of TOB2, thereby inhibiting the proliferation and invasion of breast cancer cells.

OBJECTIVE: To investigate the mechanism of shikonin-induced death of human hepatocellular carcinoma SMMC-7721 cells. METHODS: Cultured SMMC-7721 cells and normal hepatocytes (L-02 cells) were treated with 4, 8, or 16 μmol/L shikonin, and the changes in cell viability was assessed using MTT assay. The levels of ATP and lactic acid in the cell cultures were detected using commercial kits. Co-immunoprecipitation and immunofluorescence staining were used to determine the relationship among pyruvate kinase M2 (PKM2), prolyl hydroxylase 3 (PHD3), and hypoxia-inducible factor-1α (HIF-1α). The expressions of PHD3, PKM2, HIF-1α, Bax, cleaved caspase-3, and Bcl-2 in SMMC-7721 cells were detected with Western blotting, and cell apoptosis was analyzed with annexin V-FITC/PI staining. The effects of RNA interference of PKM2 on PHD3 and HIF-1α expressions in SMMC-7721 cells were detected using Western blotting. RESULTS: The IC₅₀ of shikonin against SMMC-7721 and L-02 cells was 8.041 μmol/L and 31.75 μmol/L, respectively. Treatment with shikonin significantly inhibited the protein expressions of PKM2, HIF-1α and PHD3 and nuclear translocation of PKM2 and HIF-1α in SMMC-7721 cells. Coimmunoprecipitation and immunofluorescence staining confirmed that shikonin inhibited the formation of PKM2/PHD3/HIF-1α complex and significantly reduced the contents of lactic acid and ATP in SMMC-7721 cells (P < 0.05). The expressions of PHD3 and HIF-1α decreased significantly after PKM2 knockdown (P < 0.05). Shikonin treatment significantly increased the apoptosis rate, enhanced the expressions of Bax and cleaved caspase-3, and decreased Bcl-2 expression in SMMC-7721 cells (P < 0.05). CONCLUSIONS Shikonin induces apoptosis of SMMC-7721 cells possibly by inhibiting aerobic glycolysis through the PKM2/PHD3/HIF-1α signaling pathway to cause energy supply dysfunction in the cells.
Humans ; Prolyl Hydroxylases ; Carcinoma, Hepatocellular ; Caspase 3 ; bcl-2-Associated X Protein ; Liver Neoplasms ; Signal Transduction ; Apoptosis ; Adenosine Triphosphate