The synergistic effect of palmitic acid and glucose on inducing endoplasmic reticulum stress-associated apoptosis in rat Schwann cells.

OBJECTIVE: Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus accompanied with hyperglycemia and hyperlipidemia. Both high blood glucose and high blood lipids are key pathogenies for DPN. This research aims to investigate whether the combination of glucose (Glu) and palmitic acid (PA) played a synergistic role in the pathogenesis of DPN. MATERIALS AND METHODS: The proliferation rate of Rat Schwann cell line RSC96 cells stimulated by different concentrations of Glu and PA were analyzed by CCK-8 assay. After the IC50 was detected for each drug, the RSC96 cells were divided into control, Glu, Glu+PA, PA, and BSA groups. The apoptosis of RSC96 cells in different groups were detected by flow cytometry. The effects of Glu and/or PA on endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways were determined by Western blot and qPCR. RESULTS: Both Glu and PA showed similar inhibition on the proliferation of RSC96 cells in a dose-dependent manner. However, PA induced stronger apoptosis of RSC96 cells than glucose and significantly increased the levels of X-box-binding protein-1 (XBP1), C/EBP homologous protein (CHOP), and eIF2α phosphorylation, which are key proteins regulating endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways. The combination of Glu and PA induced the strongest apoptosis in RSC96 cells and also activated ER stress-associated apoptotic signaling pathways. These results verified the synergistic effect of Glu and PA on inducing ER stress-associated apoptosis in RSC96 cells, and PA even induced stronger apoptosis in RSC96 cells than Glu. CONCLUSIONS: The present research indicated that hyperglycemia and hyperlipidemia might exert a synergistic damage during the pathogenesis of DPN, suggesting that blood lipid control is as important as blood glucose control for DPN patients.

[Analysis of pancreatic segmentation algorithm based on deep learning to improve pancreatic critical region segmentation ability on dual-phase CT].

Objective: To investigate the segmentation effects of the deep learning method on CT in the arterial phase and venous phase respectively by using subjective and objective evaluation system, and to investigate the factors that affect the difference between arterial phase and venous phase pancreas segmentation and the related factors affecting the venous pancreas segmentation. Method: A total of 218 cases of pancreatic CT scan data in the Department of Radiology of Peking Union Medical College Hospital from January to November 2019 were retrospectively collected. Each case contained images of arterial and venous phases, and the data were randomly divided into training set (139 cases), validation set (20 cases) and test set (59 cases) according to the ratio of the training and verification set to the test set of 7∶3. The two-stage global local progressive fusion network was trained on the training set, the model parameters of the optimal segmentation effect were found on the validation set, and the test set was predicted and the results were evaluated subjectively and objectively. The Likert 5-point scale was used for subjective evaluation based on the critical regions between pancreas and peripheral organs, while the Dice similarity coefficient (DSC) was used for objective evaluation. The paired t test or Wilcoxon paired rank test was used to compare the differences of subjective and objective scores of the arterial phase and venous phase. Results: For the critical regions of the pancreas at the duodenum, duodenal jejunal flexure, left adrenal gland, portal vein, superior mesenteric vein, splenic artery and splenic vein, the median number of subjective scores in arterial phase were 4(4, 5), 5(4, 5), 5(4, 5), 4(4, 5), 5(4, 5), 5(5, 5) and 4(3, 5)points respectively, the median number(first quartile, third quartile) of subjective scores in venous phase were 4(4, 4), 5(4, 5), 5(4, 5), 5(4, 5), 5(5, 5), 4(3, 4) and 5(5, 5) points respectively,there were statistically significant differences of the median number(first quartile, third quartile) of the subjective scores between the arterial and venous phase for the critical regions of the pancreas at the organs described above (all P<0.05). DSC in the venous phase was slightly higher than that in the arterial phase and the difference was not statistically significant (DSC: 0.932 vs 0.921, P=0.952). Subjective scores in venous phase of the pancreas and duodenal jejunum, stomach, and left adrenal gland with fat gaps were 4.64,4.68 and 4.63 points respectively, and those of the group without fat gaps were 4.56,4.62 and 4.56 points respectively, there were statistically significant differences of the subjective scores in venous phase of the groups with fat gaps or not between the pancreas and the organs described above (t=2.147, 2.112, 2.277, all P<0.05). Except the spleen, the density differences between the critical regions of the pancreas and other surrounding organs were statistically significant in arterial phase and venous phase segmentation (all P<0.05). Conclusion: Dual-phase CT was used to construct a deep learning automatic pancreas segmentation model, and the segmentation effect was evaluated subjectively and objectively. Subjective evaluation was helpful to improve the ability to segment the critical regions of the pancreas in the future.

MicroRNA-203a-3p affects the biological characteristics of nasopharyngeal carcinoma by targeting vascular endothelial growth factor-C.

Nasopharyngeal carcinoma (NPC) has a high incidence in Southeast Asia and China. This study aims to investigate the effect of miR-203a-3p and vascular endothelial growth factor-C (VEGF-C) on nasopharyngeal carcinoma. In this study, we investigate the transfection of miR-203a-3p mimics and the ability of miR-203a-3p to inhibit in nasopharyngeal carcinoma cell line 5-8F and C666-1, the expression levels of protein AKT, p-AKT in VEGF-C and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signal pathway by plate clone formation experiment, flow cytometer PI staining method, transwell cell experiment, vasculogenic mimicry experiment, and Western blot. The results showed that miR-203a-3p in the nasopharyngeal carcinoma cell line significantly decreased, while VEGF-C in nasopharyngeal carcinoma tissues and cell lines significantly increased. Furthermore, miR-203a-3p inhibited the proliferation of nasopharyngeal carcinoma cells and blocked the cell cycle of nasopharyngeal carcinoma in the G0/G1 phase, reduced the vasculogenic phenomena and epithelial-mesenchymal transition of nasopharyngeal carcinoma cells, and effectively inhibited the growth of nasopharyngeal carcinoma in vivo. The low expression of VEGF-C can inhibit the proliferation, vasculogenic mimicry, and epithelial-mesenchymal transition of nasopharyngeal carcinoma cells. We found that miR-203a-3p was expressed to a low degree in nasopharyngeal carcinoma. Furthermore, miR-203a-3p regulated the PI3K/AKT signal pathway by downregulating the expression of VEGF-C, thereby inhibiting the proliferation, migration, invasion, vasculogenic mimicry, epithelial-mesenchymal transition, and other malignant biological characteristics of nasopharyngeal carcinoma cells.

Coexistence of bistable multi-pulse chaotic motions with large amplitude vibrations in buckled sandwich plate under transverse and in-plane excitations.

This paper researches the dynamic snap-through phenomena and the coexistence of the multi-pulse jumping chaotic dynamics in bistable equilibrium positions and the large amplitude nonlinear vibrations for a simply supported buckled 3D-kagome truss core sandwich rectangular plate under combined transverse and in-plane excitations based on the extended high-dimensional Melnikov method. According to the two-degree-of-freedom non-autonomous nonlinear dynamical system of the buckled truss core sandwich rectangular plate and the theory of normal form, it is found that some nonlinear terms have less effects on the nonlinear dynamic responses than other nonlinear terms. The extended high-dimensional Melnikov method is employed to investigate the dynamic snap-through phenomena and the bistable multi-pulse jumping chaotic vibrations around the upper-mode and the lower-mode for two different cases of buckling in the truss core sandwich rectangular plate. A numerical method is used to detect the bistable multi-pulse jumping chaotic vibrations around two stable equilibrium positions for the non-autonomous buckled truss core sandwich rectangular plate. The obtained theoretical and numerical results indicate that there exists the coexistence of the bistable multi-pulse jumping chaotic vibrations and the large amplitude nonlinear vibrations in the buckled truss core sandwich rectangular plate under combined transverse and in-plane excitations.

Effect of inhibition to Yes-related proteins-mediated Wnt/ß-catenin signaling pathway through miR-195-5p on apoptosis of gastric cancer cells.

OBJECTIVE: This clinical study aimed to explore the expression of miR-195-5p and Yes-associated protein (YAP) in gastric cancer (GC) and their relevant apoptosis mechanism. PATIENTS AND METHODS: Thirty GC patients treated in our hospital were enrolled as a patient group and 30 normal people who underwent physical examination during the same period were enrolled as a normal group. The purchased GC cells and human gastric mucous membrane cells were used to transfect miR-195-5p-mimics, miR-NC, si-YAP, and si-RNA into MKN45 and SGC7901 cells. qRT-PCR was used to detect the expression of miR-195-5p and YAP in samples, and WB was used to detect the expression of YAP, Caspase-3, Caspase-9, ß-catenin, c-myc, and cyclin Dl. CCK-8, the transwell, and the flow cytometry were used to detect cell proliferation, invasion, and apoptosis. The dual fluorescent enzyme reporter was used to determine the relationship between miR-195-5p and YAP. RESULTS: MiR-195-5p was lowly expressed in the tissues and serum of patients, but YAP was highly expressed, and the area under the miR-195-5p and YAP curves was more than 0.9. MiR-195-5p and YAP were associated with tumor diameter, TNM stage, lymph node metastasis, and differentiation in GC patients. The overexpression of miR-195-5p and the inhibition of YAP expression can inhibit cell proliferation and invasion and promote apoptosis. WB assay showed that the overexpression of miR-195-5p and the inhibition of YAP could inhibit the expression of ß-catenin, c-myc, and cyclin D1 protein and promote the expression of Caspase-3, Caspase-9 protein. The dual fluorescent enzyme reporter revealed that there was a targeting relationship between miR-195-5p and YAP. CONCLUSIONS: The overexpression of miR-195-5p can inhibit YAP-mediated Wnt/ß-catenin signaling pathway and promote cell apoptosis, so it may be a potential therapeutic target for GC.

[Acquisition and the immunogenicity of the outer membrane FomA protein of Fusobacterium nucleatum].

Objective: To express and purify outer membrane protein FomA of Fusobacterium nucleatum (Fn) through gene recombination technique with Escherichia coli (Ec) expression system, and to detect the immunogenicity and the immune effects of the recombinant protein on gingival tissues. Methods: The gene recombination technique and Ec expression system were used to express and purified the FomA protein. Totally 20 C57 mice were immuned with the protein or the phosphate buffer solution (PBS) buffer by subcutaneous injection (each 10 mice), and the specific FomA antibody was detection in mice serum. The immunogenicity of FomA protein was assessed by comparing the differences between groups. Furthermore, the model of mice gum abscess was constructed with Fn or Fn and Porphyromonas gingivalis (Pg) mixed suspension used the above mice. The score of the gingival abscess was recorded and the interleukin (IL)-1ß in gum tissue and mice serum was determined by enzyme-linked immunosorbent assay method, and the differences of the indexes between groups were compared to evaluate the effect of the FomA protein immunization. Results: Totally 1.0-1.5 g FomA protein were successfully obtained and the protein purity was over 90%. The FomA specific antibody was detected in the serum of mice by subcutaneous injection of the protein, and the antibody titer reached the highest level in 2 weeks after secondary immunization. The model of submaxillary gingival abscess was successfully constructed. In the Fn model, the score of the FomA protein immune group was (1.82±0.35), and the PBS control group was (2.62±0.71), with statistically significant difference between the two groups (P=0.049). In the Fn+Pg mixture model, the score of gingival abscess in the FomA immune group (2.31±0.55) was lower than that in PBS group (3.63±0.45), and the difference was statistically significant (P=0.003). Both in Fn and Fn+Pg injection group, the concentration of IL-1ß in the serum of FomA immune mice and gingival tissues was lower than that of PBS control mice (P<0.001). Conclusions: The recombinant FomA protein can be acquired by Ec expression system, and it can produce a certain level antibodies in the mice serum. The way of mice subcutaneously injected with the recombinant FomA protein can reduce the severity of periodontal infections caused by Fn and Pg.

LncRNA SBF2-AS1 promotes hepatocellular carcinoma metastasis by regulating EMT and predicts unfavorable prognosis.

OBJECTIVE: Recent studies have furthered our understanding of the function of long noncoding RNAs (lncRNAs) in numerous biological processes, including cancer. The present study aimed to investigate the expression of lncRNA SBF2-AS1 (SBF2-AS1) in patients with hepatocellular carcinoma (HCC) and to investigate its effect on HCC cells. PATIENTS AND METHODS: Using quantitative reverse transcription-polymerase chain reaction, we detected SBF2-AS1 expression in HCC cell lines and primary tumor tissues. The associations between SBF2-AS1 expression and the clinicopathological factors and outcome of HCC patients were statistically analyzed. MTT assay and transwell assay were performed to determine the proliferation, migration and invasion, respectively. In addition, we evaluated the activation of Mesenchymal-epithelial transition (EMT) pathway by Western blot. RESULTS: We found that SBF2-AS1 expression levels were significantly up-regulated in HCC tissues and cell lines compared with the corresponding noncancerous liver tissues and normal hepatic cell line. In addition, high SBF2-AS1 expression levels were correlated with vein invasion (p = 0.008) and TNM stage (p = 0.013). Furthermore, Kaplan-Meier survival analysis indicated that high expressions of SBF2-AS1 were correlated with shorter overall survival of HCC patients. Univariate and multivariate analysis identified high SBF2-AS1 expression as an unfavorable prognostic factor for overall survival. Further functional analysis demonstrated that knockdown of SBF2-AS1 significantly inhibited HCC cells proliferation, migration and invasion. Mechanistically, we found that SBF2-AS1 could promote the activation of EMT pathway, which was demonstrated by measuring the expression levels of EMT-related markers. CONCLUSIONS: SBF2-AS1 might be considered as a novel molecule involved in HCC development, which provides a potential therapeutic target for HCC.

[Interpretation of the fourth edition of WHO pathological classification of the thyroid tumors in 2017].

In recent years, the incidence of thyroid carcinoma gradually increased in China. The pathology diagnosis and classification was based on WHO classification of Tumors of Endocrine Organs, the third edition which published in 2004. The fourth edition, WHO classification of Tumors of Endocrine Organs was published in July 2017. Compared with the third, some important aspects (or points) were revised: the ICD-O code of hyalinizing trabecular tumor was changed from 0 to 1; three other encapsulated follicular-patterned thyroid tumors were added; the variants of well differentiation thyroid carcinoma (including papillary carcinoma and follicular carcinoma ) which was originated from thyroid epithelial cells were updated; oncocytic cell tumors were separated from follicular tumors; the ICD-O code of ectopic thymoma was changed from 1 to 3. Refinement and standardization part of the concepts and diagnostic criterias were done which can solve practical problems in pathology diagnosis.

Idarubicin-intensified haploidentical HSCT with GvHD prophylaxis of ATG and basiliximab provides comparable results to sibling donors in high-risk acute leukemia.

We designed a novel haploidentical hematopoietic stem cell transplantation (haplo-HSCT) system using idarubicin (IDA) intensified conditioning regimens and combination of antithymocyte globulin and basiliximab for GvHD prophylaxis. The outcomes of 110 high-risk acute leukemia patients undergoing haplo-HSCT were compared with 69 contemporaneous high-risk patients receiving HLA-matched sibling transplantation using uniform IDA-intensified regimens. The relapse incidence of haplo-HSCT was 23.4%, and 3-year overall survival (OS) and disease-free survival (DFS) achieved 62.9%, 59.1%, respectively. The cumulative incidences of II-IV and III-IV aGvHD were 28.6 and 14.3%, while limited and extensive cGvHD were 19.4, 13.8%. All these results were equivalent to those of concurrent identical sibling transplantation. Three-year OS and DFS for patients in advance stage reached 48.5, 47.3%. Furthermore, the relapse, 3-year OS of positive minimal residual disease (MRD) patients did not differ from negative MRD patients (18.9% vs 11.5%, 63.6% vs 69.6%), indicating our intensified haplo-HSCT technique could circumvent the dismal prognosis of MRD. These data provide reinforcing evidence that our haplo-HSCT system could dramatically improve the survival of high-risk acute leukemia with low relapse and acceptable transplantation-related mortality, and might be a promising therapeutic option for high-risk patients.

[Effects of infant feeding practice on eczema during early childhood in Shanghai, Hohhot, and Fuzhou].

Objective: To estimate the prevalence of eczema in early childhood and effect of infant feeding practice on eczema by different regions of China with diverse climate and dietary patterns. Method: A questionnaire survey was conducted from June 2012 to October 2012 in Shanghai, Hohhot, and Fuzhou. The parent or guardian of the children aged between 2.5 to 3.5 years attending routine health visit in the chosen communities were invited to complete a modified questionnaire of the International Study of Asthma and Allergy in Childhood (ISAAC). Logistic regression model was used to analyze of the family history of allergy, duration of breastfeeding, timing of introduction of complementary foods and other potential confounders. Result: A total of 2 242 children were interviewed, 750 from Shanghai, 716 from Hohhot, and 776 from Fuzhou. The prevalence of eczema in early childhood was significantly different among Shanghai (16.9%, 95%CI 16.87-16.93), Hohhot (34.5%, 95%CI 34.46-34.54)and Fuzhou (44.3%, 95%CI 44.26-44.34). The difference was statistically significant between 3 groups (χ2=72.05, P<0.05). Introducing complementary food after the age of 6 months was associated with a decreased risk for eczema when compared to introduction between 4 to 6 months(odds ratio (OR) 0.58, 95%CI 0.41-0.81) in Fuzhou, while there was no significant association between timing of introduction of complementary foods and eczema in Shanghai and Hohhot. Conclusion: The prevalence of eczema during early childhood is various among three cities. The relationship between timing of introduction of complementary foods and eczema in Fuzhou is different from that in Shanghai and Hohhot. The role of climate and dietary patterns on prevalence of eczema needs further studies.

Antibody detection tests for early diagnosis in tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Microbiological confirmation is rare and treatment is often delayed. Early diagnosis and immediate initiation of treatment are essential for effective TBM control. A systematic review was performed in this study to assess the diagnostic accuracy of detecting antibodies against Mycobacterium tuberculosis in the cerebrospinal fluid (CSF), according to standard methods. Test performance was summarized using a bivariate random-effects meta-analysis. METHODS: Studies were identified by a search of the literature, up to July 25, 2015, in the EMBASE and MEDLINE databases via Ovid SP and PubMed. The Cochrane Library was also searched for original, peer-reviewed molecular epidemiology studies that reported the diagnosis of TBM based on antibody detection in the CSF. RESULTS: Thirty-six articles (58 studies) were identified. The sensitivity of antibody detection was 0.75 (95% confidence interval (CI) 0.66-0.82), specificity was 0.98 (95% CI 0.96-0.99), and the area under the receiver operating characteristic curve (AUROC) was 0.97 (95% CI 0.95-0.98). By subgroup analysis, the detection of anti-M37Ra was the highest (AUROC 0.99, 95% CI 0.98-1.00), followed by anti-antigen 5 (AUROC 0.99, 95% CI 0.97-0.99) and anti-M37Rv (AUROC 0.97, 95% CI 0.95-0.98). CONCLUSIONS: For the early diagnosis of TBM based on antibodies in the CSF, the detection of anti-M37Ra, anti-antigen 5, or anti-M37Rv provides the greatest sensitivity and specificity.

piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma.

Aberrant DNA hypermethylation contributes to myelomagenesis by silencing tumor-suppressor genes. Recently, a few reports have suggested that a novel class of small non-coding RNAs, called Piwi-interacting RNAs (piRNAs), may be involved in the epigenetic regulation of cancer. In this study, for the first time we provided evidence that the expression of piRNA-823 was upregulated in multiple myeloma (MM) patients and cell lines, and positively correlated with clinical stage. Silencing piRNA-823 in MM cells induced deregulation of cell cycle regulators and apoptosis-related proteins expression, accompanied by inhibition of tumorigenicity in vitro and in vivo. Moreover, piRNA-823 was directly relevant to de novo DNA methyltransferases, DNMT3A and 3B, in primary CD138(+) MM cells. The inhibited expression of piRNA-823 in MM cells resulted in marked reduction of DNMT3A and 3B at both mRNA and protein levels, which in turn led to decrease in global DNA methylation and reexpression of methylation-silenced tumor suppressor, p16(INK4A). In addition, piRNA-823 abrogation in MM cells induced reduction of vascular endothelial growth factor secretion, with consequent decreased proangiogenic activity. Altogether, these data support an oncogenic role of piRNA-823 in the biology of MM, providing a rational for the development of piRNA-targeted therapeutic strategies in MM.

Highly stable sub-5 nm Sn6O4(OH)4 nanocrystals with ultrahigh activity as advanced photocatalytic materials for photodegradation of methyl orange.

Among numerous active photocatalytic materials, Sn-based oxide nanomaterials are promising photocatalytic materials in environmental protection measures such as water remediation due to their excellent physicochemical property. Research on photocatalytic nanomaterials for photodegradation of methyl orange (MO) so far has focused on TiO2-based nanostructures; e.g., TiO2-P25 is recognized to be the best commercial photocatalyst to date, rather than Sn-based oxide nanomaterials, in spite of their impressive acid- and alkali-resistant properties and high stability. Here, we demonstrate very high photocatalytic activity of highly stable sub-5 nm hydromarchite (Sn6O4(OH)4) nanocrystals synthesized by a simple and environmentally friendly laser-based technique. These Sn6O4(OH)4 nanocrystals exhibit ultrahigh photocatalytic performance for photodegradation of MO and their degradation efficiency is far superior to that of TiO2-P25. The detailed investigations demonstrated that the great photocatalytic activity results from the ultrafine size and unique surface activity induced by the laser-based technique. Mass production of reactive species of hydroxyl radicals was detected in the experiments due to the appropriate bandgap of Sn6O4(OH)4 nanocrystals. These findings actually open a door to applications of Sn-based oxide nanomaterials as advanced photocatalytic materials.

Epidemiology of traumatic cervical spinal cord injury in Tianjin, China.

STUDY DESIGN: A retrospective epidemiological study. OBJECTIVE: To describe the recent epidemiological characteristics of traumatic cervical spinal cord injury (TCSCI) in adults in Tianjin. SETTING: Tianjin Medical University General Hospital. METHODS: This study included all TCSCI patients aged ≥ 15 years who were admitted to a general hospital from December 2008 to November 2011. Epidemiological characteristics including gender, age, marital status, occupation, etiology, level of injury, severity and America Spinal Injury Association (ASIA) impairment scale were recorded. RESULTS: A total of 143 patients with TCSCI were included in the study. Mean age was 54.6 ± 14.6 years (men 53.5 ± 14.9 years, women 54.2 ± 12.1 years), with a range of 18-87 years, and the male/female ratio was 5:1. The leading cause was falls (49.7%), followed by motor vehicle accidents (36.4%). The most common injury site was C5, accounting for 42%. In all, 74 (51.7%) patients had complications; the most common complication was hyponatremia (30.1%), followed by urinary infection (23.1%), respiratory infection (18.2%), bedsore (9.8%) and deep venous thrombosis (4.9%). As for the severity, ASIA grade D was encountered most frequently. Six patients died, five of whom died from respiratory failure. CONCLUSION: The epidemiology of TCSCI has its own characteristics. Falls were the leading causes, and TCSCI occurred most frequently in the middle-aged and elders. Therefore, establishing public policies aimed at preventing injuries should focus on falls and more attention should be paid to the aged regarding their vulnerability to low fall. Additionally, complications should be prevented in TCSCI patients.

Expression of beclin 1, an autophagy-related protein, in human cervical carcinoma and its clinical significance.

PURPOSE: To investigate the impact of beclin 1 on prognosis of cervical cancer, we determined the expression of beclin 1 in cervical cancer, cervical intraepithelial neoplasia (CIN) and normal cervical tissues. METHODS: A total of 122 cases of cervical cancer, 35 cases with CIN and 31 cases with uterine fibroids were collected at the Cancer Center of Sun Yat University to determine the expression of beclin 1. RESULTS: Beclin 1 positive rate in normal cervical tissues, CIN tissues and cervical cancers was 83.9%, 74.3% and 53.3%, respectively, and it was significantly different between the three groups (p < 0.01). Beclin 1 expression was negatively correlated with cervical cancer differentiation, lymph node metastasis, recurrence and death (p < 0.05). The negative expression is the risk factor affecting overall survival (p < 0.05) and progression-free survival (PFS) (p < 0.05). Multivariate analysis showed that beclin 1 negative expression was an independent risk factor of PFS time. CONCLUSIONS: Beclin 1 may play a role in the occurrence and development of cervical cancer. Beclin 1 positive expression in patients indicates a better prognosis.

Angiopoietin-2 inhibits the growth of tongue carcinoma without affecting expression of vascular endothelial growth factor.

Angiopoietin-2 (Ang-2) has been identified as an important factor in tumour angiogenesis through its action in blocking the stabilizing actions of Ang-2 and leading to new tumour vessel growth in the presence of vascular endothelial growth factor (VEGF). In the authors' previous study, over-expression of Ang-2 in Tca8113 tongue tumour cells inhibited growth. The current study aims to clarify the mechanisms of Ang-2-mediated tumour growth inhibition and its role in the regulation of VEGF expression. These studies used tumours derived from Ang-2-transfected Tca8113 cells injected into nude mice. The results showed that Ang-2-transfected tumours displayed aberrant angiogenic vessels with few associated smooth muscle cells. No detectable differences in VEGF expression were observed between Ang-2-transfected and parental tumours. Tumours produced by the Ang-2 transfection also had a higher apoptosis index and lower tumour cell proliferative index than tumours in the control groups. These observations suggest that enhanced expression of Ang-2 has no effect on VEGF expression and results in tumour vessel regression and inhibition of tumour growth.

Nestin expression in different tumours and its relevance to malignant grade.

BACKGROUND: Nestin, an intermediate filament (IF) protein, is expressed in proliferating progenitor cells of developmental and regenerating tissues, and is identified as a neuroepithelial precursor cell marker. Recently, nestin was detected in some neoplasms such as glioma, ependymoma, melanoma, rhabdomyosarcoma, gastrointestinal stromal tumour (GIST), and testicular stromal tumour. Moreover, the expression intensity of nestin exhibited significant correlation with the malignant grade of glioma. AIMS: To detect the expression of nestin in different tumours and to analyse the relationship between the expression of nestin and the malignant grade of the tumours. METHODS: Formalin-fixed and paraffin-embedded surgical samples of neoplastic tissues were obtained from the Department of Pathology of Sun Yat-sen University. Histological analysis and immunohistochemical staining for nestin were performed. Histoscores were analysed by semi-quantitative evaluation. RESULTS: Nestin was expressed predominantly in the cytoplasm of angiosarcoma, pancreatic adenocarcinoma and GIST samples, and some tumour cells expressed in the nucleus. There was a statistically significant difference between the histoscore of nestin in high malignant GIST (2.2366 (0.6920)) and that in low malignant GIST (1.3783 (0.4268)) (p = 0.003); and also between that in high malignant angiosarcoma (1.9188 (0.2069)) and that in low malignant angiosarcoma (0.6474 (0.3273)) (p = 0.000). Cavernous angioma did not express nestin. The histoscore of nestin in high malignant pancreatic adenocarcinoma (7/14) was 1.1767 (0.4676), and that in low malignant pancreatic adenocarcinoma (3/8) was 0.6577 (0.0056) (no significant difference, p = 0.112). CONCLUSIONS: Results suggest that the expression of nestin may play an important role in the development of some neoplasms such as GIST and angiosarcoma.

A distinct strategy to generate high-affinity peptide binders to receptor tyrosine kinases.

We describe a novel and general way of generating high affinity peptide (HAP) binders to receptor tyrosine kinases (RTKs), using a multi-step process comprising phage-display selection, identification of peptide pairs suitable for hetero-dimerization (non-competitive and synergistic) and chemical synthesis of heterodimers. Using this strategy, we generated HAPs with K(D)s below 1 nM for VEGF receptor-2 (VEGFR-2) and c-Met. VEGFR-2 HAPs bound significantly better (6- to 500-fold) than either of the individual peptides that were used for heterodimer synthesis. Most significantly, HAPs were much better (150- to 800-fold) competitors than monomers of the natural ligand (VEGF) in various competitive binding and functional assays. In addition, we also found the binding of HAPs to be less sensitive to serum than their component peptides. We believe that this method may be applied to any protein for generating high affinity peptide (HAP) binders.

Loss of pesticides from agricultural fields in SE Norway--runoff through surface and drainage water.

Loss of two pesticides with different mobility characteristics, bentazone (Koc approximately 34) and propiconazole (Koc approximately 1800), were studied at three agricultural fields (Askim, Bjørnebekk and Syverud) in SE Norway. A conservative tracer (Br) was used to follow the flow of water. The loss of pesticides varied among the fields, depending on hydrological characteristics and soil properties. The loss of pesticides was higher from two artificially levelled silty clay loam soils with poor aggregate stability (Askim and Bjørnebekk) compared to a loam/silt loam soil with increased content of organic carbon and better aggregate stability (Syverud). The total accumulated loss was <0.5% from all fields. The highest pesticide concentrations were measured at the first runoff episode after application for both the mobile (bentazone) and less mobile pesticide (propiconazole) in the surface runoff. In the drainage water, the peak for the less mobile pesticide coincided with the Br tracer, while the peak for mobile pesticide appeared earlier than the Br tracer. Rapid movement of water, particles and pesticides through soils indicate flow through macropores. Larger proportions (in percent of total applied) of both the mobile and the strongly sorbed pesticides were lost through the drainage as compared to the loss through surface runoff at Askim. Here, it is suggested that macropore flow contribute to the increased loss of pesticides through the drainage. At Syverud, high infiltration capacity reduces the amount of water available for surface runoff, and somewhat higher loss of the mobile pesticide was registered in the drainage compared to the surface runoff. For the strongly sorbed pesticide, however, propiconazole was neither detected in surface nor in drainage water at Syverud. Generally, there was a higher percentage loss of the mobile compared to the strongly sorbed pesticide in both surface and drainage water, which is in agreement with the pesticides mobility characteristics in soil. An exception was, however, the erodible soil Bjørnebekk, where a higher fraction of propiconazole was lost in the surface runoff compared to bentazone. Large amounts of sediment transport from the Bjørnebekk field probably contributed to enhanced transport of the strongly sorbed pesticide.

Prevalence of human papillomavirus in cervical cancer: a multicenter study in China.

A large-scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV-16 was present in 79.6%, HPV-18 in 7.5%, HPV-52 in 2.6% and HPV-58 in 3.8% of all HPV-positive specimens. The prevalences of HPV-16 and HPV-18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV-16 and a higher HPV-18 proportion compared with the other regions. HPV-16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV-18 infection was significantly higher in AC than in SCC.