A compact radio-frequency ion source for high brightness and low energy spread negative oxygen ion beam production.

A high brightness and low energy spread (∆E) ion source is essential to the production of a high-quality primary ion beam applied in secondary ion mass spectrometry (SIMS). A compact 13.56 MHz radio-frequency (RF) ion source with an external planar spiral antenna has been developed as a candidate ion source for the production of negative oxygen ion beams for SIMS application. This ion source is designed with a three-and-a-half-turn water-cooled planar antenna for RF power coupling, a multi-cusp magnetic field for effective plasma confinement, and a three-electrode extraction system. The experimental results show that more than 50 µA negative oxygen ion beams have been extracted, which consist of 56% O-, 25% O2-, and 19% O3-. The ion energy distribution of the negative oxygen ion beam exhibits a Gaussian distribution with a minimum ∆E of 6.3 eV. The brightness of the O- beam is estimated to be 82.4 A m-2 Sr-1 V-1. The simulation, design, and experimental study results of this RF ion source will be presented in this paper.

[Analysis of 53 cases of transjugular liver biopsy].

Objective: To investigate the practicability and safety of transjugular liver biopsy (TJLB). Methods: Data of 53 cases with transjugular liver biopsy from June 2015 to June 2020 were collected. LABS-100 was used in all patients who underwent transjugular liver biopsy. Among them, 45 cases and eight were biopsied via hepatic vein and intrahepatic segment of the inferior vena cava. The surgical indications, related complications, and postoperative pathological diagnosis were analyzed and summarized. Results: TJLB was successful in all patients, with an average of 2.8 punctures per case. Satisfactory liver tissue and histopathological diagnosis was obtained in all patients. Two cases developed a cervical hematoma that was improved spontaneously, and one patient developed an intrahepatic hematoma that was improved after conservative treatment. Conclusion: TJLB is a practical and safe method for patients with contraindications to percutaneous liver biopsy.

[Comparison of hereditary breast and ovarian cancer syndrome and sporadic ovarian cancer in ovarian cancer BRCA mutations].

Objective: To study the difference between BRCA gene mutations in hereditary breast and ovarian cancer syndrome (HBOC) and in sporadic ovarian cancer (SOC). Methods: This study was for exploratory research, the inclusion criteria were 284 patients with ovarian cancer admitted at Shanxi Provincial Cancer Hospital from November 2018 to December 2019, with high-throughput DNA sequencing including the full coding regions and exon-intron link regions of BRCA1 and BRCA2 gene. Pathogenic mutations in the BRCA gene of patients with ovarian cancer were collected and mutation site analysis was performed to compare phenotypic differences in pathogenic mutations between HBOC syndrome and SOC patients. Results: (1) Of the 284 ovarian cancer patients, seventy-seven had BRCA pathogenic mutations with a mutation rate of 27.1% (77/284), with BRCA1 mutation rate of 19.7% (56/284), BRCA2 gene 6.7% (19/284) and BRCA1/2 common mutation rate of 0.7% (2/284). Of the 284 patients with ovarian cancer, the pathogenic mutation rate in the BRCA gene in HBOC syndrome patients was 43.8% (32/73), which were significantly higher than that in SOC patients [21.3% (45/211); χ²=13.905, P<0.01]. Among BRCA1 gene mutation, the mutation rate in HBOC syndrome was higher than that of SOC [87.5% (28/32) vs 62.2% (28/45)], the BRCA2 gene mutation rate in patients with HBOC syndrome was lower than that in SOC patients [6.2% (2/32) vs 37.8% (17/45)], and there were statistically significant differences (all P<0.05). Two of the 77 patients with pathogenic mutations in the BRCA gene were multisite mutations, including one simultaneous two site mutation, one simultaneous three site mutation. There were 80 mutation sites with frameshift deletion mutations (55.0%, 44/80) and nonsense mutations (31.2%, 25/80). (2) Of the 73 patients with HBOC syndrome, 32 cases had pathogenic mutations in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (9 and 7 cases, respectively), and only two cases in BRCA2, both in exon 11; another two had multiple locus mutations. Of the 211 patients with SOC, 45 cases had pathogenic mutants in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (15 and 2 cases, respectively), and 17 cases in BRCA2, mainly in exon 11 (11 cases). (3) Thirty-four pathogenic mutation sites in BRCA gene were found newly, twenty of them were located in the BRCA1 gene, including a locus located on the intron 6, 301+1G>A, and the remaining 19 sites were located on the exons, including 283_286delCTTG, 68_69delAG, 132C>T, 514_547+3del37, 742delA, 1126_1129delAATA, 1196delA, 1352_1364del, 1465G>T, 2171delC, 2341G>T, 3359_3363delTTAAT, 4085_4086ins11, 4161_4162delTC, 4165_4166delAG, 4258G>T, 4338_4339del8insAGAA, 4468G>T, and 4783delA; fourteen sites were located in the BRCA2 gene, including a locus located on the intron 7, 631+1G>A, and the remaining 13 sites were located on the exons, including 2648delT, 2914A>T, 2950_2951insG, 4357+1G>A, 5054C>T, 5257A>T, 5291_5292insTC, 5913delT, 3593delA, 6091_6092insA, 6135_6136delTT, 7452delT, 9097_9098insA. A tal of 28 repeat mutations were located in the BRCA1 gene; among them, the site 5470_5477del8 was repeated 6 times, while 3 times in 981_982delAT. Conclusions: Patients with HBOC syndrome have a significantly higher rate of pathogenic mutation in the BRCA gene than that in patients with SOC. BRCA gene pathogenic mutation sites in HBOC syndrome patients occur commonly in exon 11 and 24 of BRCA 1 gene, while SOC patients occur mainly in exon 11 and 24 of BRCA1 gene and exon 11 of BRCA2 gene. The two loci of BRCA1∶5470_5477del8, BRCA1∶981_982delAT may be ancestor mutations in Chinese ovarian cancer patients, and 34 newly discovered pathogenic mutations in the BRCA gene, enriching the BRCA gene mutation spectrum in the Chinese population.

Metformin reduces pancreatic cancer cell proliferation and increases apoptosis through MTOR signaling pathway and its dose-effect relationship.

OBJECTIVE: To study the influences of metformin on the proliferation and apoptosis of pancreatic cancer cells and its dose-effect relationship and crucial molecular mechanism. MATERIALS AND METHODS: With human pancreatic cancer cell line PANC-1 as the study object, different concentrations of metformin were added for intervention. Then, the proliferation of PANC-1 cells was detected via methyl thiazolyl tetrazolium (MTT) assay to determine the dose-effect relationship of metformin in PANC-1 cell proliferation. PANC-1 cells were treated with metformin at three appropriate concentrations as Metformin treatment groups, and an equal amount of dimethyl sulfoxide (DMSO) was added in Control group. Flow cytometry was performed to detect PANC-1 cell cycle and apoptosis, and the apoptosis of PANC-1 cells was also evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Caspase-3 protein localization and expression in PANC-1 cells were detected using immunofluorescence assay. Besides, the expressions of the apoptosis-associated proteins Caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2 associated X protein (Bax) and phosphatidylinositol 3-hydroxy kinase (PI3K), phosphorylated protein kinase B (p-Akt), and p-mammalian target of rapamycin (mTOR) proteins related to the mTOR pathway were detected using Western blotting. RESULTS: Metformin repressed the proliferation of human pancreatic cancer PANC-1 cells in a concentration-dependent and time-dependent manner. Compared with Control group, Metformin treatment groups (0, 20 and 40 mM) exhibited a higher proportion of PANC-1 cells in G0/G1 phases, and a lower proportion of PANC-1 cells in S phase (p<0.05), and the change in the proportion of cells in G2/M phase was not statistically significant (p>0.05). Moreover, Metformin treatment groups (0, 20, and 40 mM) had more apoptotic PANC-1 cells, higher expression levels of pro-apoptosis proteins Caspase-3 and Bax and lower expression levels of anti-apoptosis protein Bcl-2 and the mTOR pathway-related proteins PI3K, p-Akt, and p-mTOR in cells than Control group (p<0.05). CONCLUSIONS: Metformin modulates the mTOR signaling pathway to reduce the proliferation of pancreatic cancer cell, but increase their apoptosis.

Intense carbon beams production with an all permanent magnet electron cyclotron resonance ion source for heavy ion medical machine.

LAPECR3 (Lanzhou All Permanent magnet Electron cyclotron Resonance ion source No. 3) had been developed as an ion injector of Heavy Ion Medical Machine (HIMM) accelerator facility since 2009. The first HIMM accelerator facility was built in Wuwei city in 2015, and the LAPCER3 ion source has delivered C5+ ion beam to HIMM for more than 1000 days in the past four years. In order to improve the performance of the LAPECR3 ion source for intense carbon beams production, continuous research and development work has been made. The recently developed LAPECR3 ion source together with the new low-energy beam transportation can provide better performance in terms of both beam intensity and quality. This paper will generally review the LAPECR3 ion source operation status for HIMM, and the recent improvement will be presented, especially the stable beams production of C4+ and C5+.

Laser ablation plasma with solenoid field confinement.

A Laser Ion Source (LIS) can produce high charge state and high intensity ion beams (∼emA), especially, refractory metallic ion beams, which makes it a promising candidate as an ion source for heavy ion cancer therapy facilities and future accelerator complexes, where pulsed high intensity and high charged heavy ion beams are required. However, it is difficult for the LIS to obtain a long pulse width while ensuring high current intensity, thus limiting the application of the LIS. To solve the conflict, magnetic fields are proposed to confine the expansion of the laser produced plasma. With a solenoid along the normal direction to the target surface, the lateral adiabatic expansion of the laser ablation plasma is suppressed which extends the pulse width of the ion beam effectively. The characteristics of laser ablation plasma with solenoid field confinement will be presented and discussed in this paper.

[Trend in proportion and clinicopathological characteristics of young women with stage â a2 to â ¡a2 cervical cancer].

Objective: To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods: The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results: (1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004-2010 than that during 2011-2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ(2)=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions: The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

Correlations of ultrasound and pathological features of thyroid carcinoma with TC-1 mRNA and protein expression.

OBJECTIVE: To investigate the correlations of ultrasound and pathological characteristics of thyroid carcinoma through evaluating the messenger ribonucleic acid (mRNA) level and protein expression of thyroid cancer-1 (TC-1). PATIENTS AND METHODS: The patients with papillary thyroid carcinoma (PTC) hospitalized in our hospital were enrolled. Then, real-time fluorescence quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) streptavidin-peroxidase (SP) technique were applied to measure the mRNA and protein expression levels of TC-1 in PTC and corresponding adjacent tissues (NCE) of 50 patients. The relations with clinicopathological and ultrasound characteristics were analyzed. RESULTS: The expression of TC-1 mRNA in PTC tissues was statistically higher than that in corresponding adjacent tissues and significantly correlated with tumor-node-metastasis (TNM) stage, pathological grade, and lymph node metastasis of PTC (p<0.05). According to IHC, TC-1 positive expression was mainly found in the cytoplasm in PTC samples, which was statistically increased compared to adjacent tissues (p<0.05). Western blotting results revealed that the relative protein expression of TC-1 in PTC tissues was 2.646±195, which was significantly higher than that in corresponding adjacent tissues (892±76) (p<0.05). The TC-1 protein expression also showed significant associations with TNM stage, pathological grade, and lymph node metastasis of patients (p<0.05). The level of TC-1 mRNA in PTC tissues with micro-calcification detected by ultrasound (87.46±49.55) was higher than that in those without micro-calcification (38.46±29.15) (p<0.05). CONCLUSIONS: The expression of TC-1 plays an important role in the occurrence and development of PTC. Ultrasound characteristics reflect the expression of TC-1 in PTC tissues to some extent, providing a certain value in evaluating the prognosis of PTC.

MiR-216a-5p act as a tumor suppressor, regulating the cell proliferation and metastasis by targeting PAK2 in breast cancer.

OBJECTIVE: Our study aimed to investigate the expression of microRNA-216a-5p (miR-216a-5p) in breast cancer (BC) and its effect on the proliferation and metastasis of BC cells by regulating the expression of p21-activated protein kinase 2 (PAK2) gene. PATIENTS AND METHODS: A total of 50 cases of cancer tissue specimens and corresponding para-carcinoma normal tissue specimens were collected from the breast surgery department of our hospital from July 2016 to December 2017. BC MCF-7 cell line and normal breast epithelial MCF-10A cells were cultured. MiR-NC (negative control), LV-p21-activated protein kinase 2 (PAK2) and/or miR-216a-5p mimics were synthesized and transfected. The protein and mRNA expression level in BC tissues and cells were detected by Western blot and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay, respectively. Additionally, the Luciferase Reporter Assays, cell proliferation detection, clone formation assays and transwell migration and invasion assay were performed to determine the functional alteration of BC cells, respectively. RESULTS: The results of qRT-PCR demonstrated that miR-216a-5p was decreased in both BC tissues and cells compared with that in normal controls. Online target gene prediction software and Dual-Luciferase reporter assay were used for target identification, and PAK2 was identified as a functional target of miR-216a-5p in BC cells. The results were further clarified with the Western blot (WB) experiment. In vitro, cell functions were detected by Cell Counting Kit-8 (CCK-8), crystal violet staining and transwell experiment, respectively. The results indicated that decreased expression of PAK2 resulting from the up-regulation of miR-216a-5p could restrain the proliferation, clone formation, invasion and migration abilities of BC cells. CONCLUSIONS: We showed that miR-216a-5p played a role as antioncogene in BC, which provides a new therapeutic target for the treatment of BC.

[Relationship between large artery elasticity function and coronary heart disease, lower extremity arterial disease in patients with carotid plaque].

OBJECTIVE: To evaluate the relationship between large artery elastic function and coronary heart disease (CHD) or lower extremity arterial disease (LEAD) in patients with carotid plaque. METHODS: A total of 491 patients with carotid plaque were enrolled into the study with complete data of arterial stiffness detection and blood test [male: 208 and female: 283, and mean age: (61.66±11.60) years]. All the subjects were divided into 2 groups according to CHD or LEAD, namely non-CHD&LEAD group (neither CHD nor LEAD) and CHD/LEAD group (either CHD or LEAD). Accor-ding to the mean age level (age<61.66 years or age>61.66 years), the independent association was analyzed between higher large arterial stiffness (carotid-femoral pulse wave velocity, CF-PWV, CF-PWV>9 m/s) and CHD/LEAD. RESULTS: In the present research population, the mean level of arterial stiff-ness was high (the mean CF-PWV was 10.71 m/s), and 76.6% of them had arteriosclerosis, and 36.9% CHD/LEAD. The age, male and smoking proportion, systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c), homocysteine (Hcy), creatinine (Cr), CF-PWV, prevalence rate of hypertension and diabetes mellitus, medication on hypertension, diabetes and hyperlipidemia were higher in CHD/LEAD group, and total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were lower in CHD/LEAD group than in non-CHD&LEAD group (all P<0.05).In multivariate Logistic regression analysis, the results showed that in the patients with age below 61.66 years, large artery stiffness (CF-PWV>9 m/s) was an independent risk factor of CHD/LEAD (OR=3.229, 95%CI 1.156-9.022, P<0.05); In the patients with age above 61.66 years, there was no independent association between large artery stiffness and CHD/LEAD (P>0.05). CONCLUSION: The large artery elasticity function in the patients with carotid plaque was poor. In the patients with carotid plaque and higher large artery stiffness below 61.66 years, the risk of the prevalence of CHD/LEAD was increased significantly than with normal arterial stiffness. In the patients with carotid plaque below or above 61.66 years, the independent influencing factors on the prevalence of CHD/LEAD were different.

[Effect of Δ40p53 isoform on enhancing the pro-apoptotic function of p53 in tumor cells].

Objective: To investigate the effect of Δ40p53, an alternative spliced isoform of p53 lacking the N-ter minus, on the pro-apoptotic function of p53. Methods: The wild-type p53 was ectopically expressed in HCT116-p53(-/-) (endogenous Δ40p53 expression), HCT116-p53(+ /+) (wild-type p53) and H1299 (p53-null) cells by adenoviral delivery, while Δ40p53 plasmid were transfected into these cells to overexpress Δ40p53. The levels of Δ40p53 and p53 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR. The expression of related proteins was deter mined by Western blotting. The interaction of p53 and Δ40p53 was observed by co-immunoprecipitation assay. Calcein-AM/propidium iodide (PI) staining and flow cytometry were used to detect the apoptotic rate of tested cells in each group. Results: HCT116-p53(-/-) cells expressed endogenous Δ40p53 isoform. Neither transcription nor protein expression of wild-type p53 was interfered by the increased expression of Δ40p53. Full length p53 and Δ40p53 could bind to each other. Calcein-AM/PI staining showed that the apoptotic rates of H1299-Control, HCT116-p53(-/-) -Control, H1299+ p53, HCT116-p53(-/-)+ p53, H1299+ oxaliplatin (Oxa), HCT116-p53(-/-)+ Oxa, H1299+ p53+ Oxa and HCT116-p53(-/-)+ p53+ Oxa groups were (2.50±0.47)%, (2.40±0.32)%, (5.20±0.58)%, (4.10±0.18)%, (22.40±1.73)%, (19.30±1.11)%, (29.90±1.15)% and (39.30±2.26)%, respectively. It was statistically significant between H1299+ p53+ Oxa and HCT116-p53(-/-)+ p53+ Oxa groups (t=3.721, P=0.0205). Moreover, the apoptotic rates of H1299-Control, H1299+ Δ40p53, H1299+ p53, H1299+ p53+ Δ40p53, H1299+ Oxa, H1299+ Δ40p53+ Oxa, H1299+ p53+ Oxa and H1299+ p53+ Δ40p53+ Oxa groups were (2.60±0.35)%, (2.20±0.17)%, (4.80±0.49)%, (4.90±1.10)%, (20.30±1.10)%, (19.60±1.45)%, (27.90±1.39)%, (35.20±1.43)%, respectively. Furthermore, flow cytometry assay showed that the apoptotic rates of above cells were (2.70±0.32)%, (2.20±0.24)%, (4.60±0.48)%, (3.90±0.67)%, (19.30±1.11)%, (17.70±0.66)%, (28.30±2.76)% and (37.50±1.51)%, respectively. H1299+ p53+ Δ40p53+ Oxa cells showed higher cell apoptosis than H1299+ p53+ Oxa cells (t=2.930, P=0.042). Conclusion: Δ40p53 isoform can bind to full-length p53, and enhance its pro-apoptotic function in tumor cells.

[Effect of curcumin on intestinal mucosal mechanical barrier in rats with non-alcoholic fatty liver disease].

Objective: To investigate the effect of curcumin on intestinal mucosal mechanical barrier in rats with non-alcoholic fatty liver disease. Methods: A total of 30 male Sprague-Dawley rats were equally divided into normal control group, model group, and curcumin intervention group. The rats in the model group and the curcumin intervention group were given high-fat feed for 16 weeks, and those in the curcumin intervention group were given curcumin 200 mg/kg/day by gavage once a day after 8 weeks of high-fat feeding. The rats were sacrificed at the end of week 16. A light microscope was used to observe pathological changes in the liver, an electron microscope was used to observe the tight junction of the intestinal mucosa, an automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), chromogenic substrate Limulus amebocyte lysate assay was used to measure plasma lipopolysaccharide (LPS) level, spectrophotometric method was used to measure the activity of serum diamine oxidase, ELISA was used to measure the serum level of tumor necrosis factor-α (TNFα), and immunohistochemistry was used to measure the expression of the tight junction protein occludin. One-way ANOVA test and SNK-q test were used for statistical analysis. Results: Under the light microscope, the control group had no hepatocyte steatosis, the model group had significant hepatocyte steatosis and inflammatory cell infiltration, and the curcumin intervention group had reduced hepatocyte steatosis and inflammatory cell infiltration. Under the electron microscope, the control group had a clear and complete structure of the tight junction of the intestinal mucosa and normal structures of mitochondria and endoplasmic reticulum; in the model group, the structure of the tight junction of the intestinal mucosa was destroyed, the intercellular space was widened, the desmosomes had a loose structure, there was edema in some mitochondria, and the endoplasmic reticulum was dilated; the curcumin intervention group had improvements in the structure of tight junction of the intestinal mucosa, intercellular space, edema in the mitochondria, and dilation of the endoplasmic reticulum. Compared with the control group, the model group had significant increases in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = -15.918, -14.402, -33.700, -8.944, and -10.832, P < 0.05); compared with the model group, the curcumin intervention group had significant reductions in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = 10.457, 7.752, 18.802, 5.202, and 4.279, P < 0.05). In the control group, occludin showed a linear distribution along the top of small intestinal mucosal epithelial cells. The model group had a significant reduction in positive staining compared with the control group, and the curcumin intervention group had a significant increase in positive staining compared with the model group. The relative expression of occludin was 0.29±0.03 in the control group, 0.12±0.02 in the model group, and 0.21±0.02 in the curcumin intervention group (P < 0.05). Conclusion: Intestinal mucosal mechanical barrier is impaired in rats with NAFLD. Curcumin can reduce such damage, and its mechanism of action may be related to up-regulating the expression of occludin in the intestinal mucosa and reducing the levels of TNFα and LPS.

Gene expression profiling analysis of the role of miR-22 in clear cell ovarian cancer.

This study aimed to investigate the role and potential mechanism of miR-22 in clear cell ovarian cancer (CCOC) progression. The gene expression profile of GSE16568, including 3 CCOC samples with miR-22 overexpression and 3 negative controls, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the limma package in R. Gene Ontology (GO) and pathway enrichment analysis of DEGs were performed by using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, protein-protein interaction (PPI) network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Besides, the miR-22-mRNA interaction pairs were predicted to explore the critical genes involved in the cancer. Totally, 95 up-regulated DEGs and 51 down-regulated DEGs were identified. The DEGs were enriched in different GO terms and pathways. The up-regulated genes cyclin-dependent kinases (CDK6), MDM2 oncogene, E3 ubiquitin protein ligase (MDM2), and thrombospondin 1 (THBS1) were involved in the p53 signaling pathway. The up-regulated gene FBJ murine osteosarcoma viral oncogene homolog (FOS) was a hub protein in the PPI network of the DEGs. The down-regulated DEGs including lymphoid enhancer-binding factor 1 (LEF1) and v-myb avian myeloblastosis viral oncogene homolog (MYB) were mainly associated with immunity. Nine DEGs as target genes were identified to be recognized by miR-22. Our study suggested that several key genes such as CDK6, MDM2, LEF1, MYB, and FOS that involved in different pathways including p53 signaling pathway were associated with CCOC progression. miR-22 may play an essential role in cell migration and invasion in CCOC through targeting responsive genes.

[Jaridonin, a new diterpenoid from Isodon rubescens, induces cell cycle arrest in gastric cancer cells through activating ataxia telangiectasia mutated kinase].

OBJECTIVE: To study the effects of Jaridonin, a novel diterpenoid from isodon rubescens, on the cell cycle of human gastric cancer cells and its molecular mechanism of action. METHODS: Flow cytometry was used to analyze the cell cycle distribution and expression of ataxia telangiectasia mutated kinase (ATM) after Jaridonin treatment. Western blot was performed to detect the expression of cell cycle-related proteins. RESULTS: The results of flow cytometry showed that the percentages of MGC-803 cells in G(2)/M phase at 6 hours after 0, 10, 20 µmol/L Jaridonin-treatment were (10.8±2.2)%, (18.2±2.5)%, (27.3±3.2)%, respectively; those at 12 hours after Jaridonin-treatment were (12.0±1.5)%, (24.1±2.0)% and (39.7±5.2)%, respectively, indicating a G2/M phase arrest of MGC-803 cells was resulted in a time- and dose-dependent manner. The expressions of ATM, Chk1, Chk2, phosphorylated Cdc2 and CDK2 were up-regulated in the MGC-803 cells after Jaridonin treatment, while the levels of Cdc2 and CDK2 were decreased. KU-55933, an inhibitor of ATM, reversed the expression of relevant proteins and G(2)/M phase arrest induced by Jaridonin. CONCLUSIONS: Jaridonin can significantly induce G(2)/M arrest in gastric cancer MGC-803 cells. Its mechanism may be related to the activation of ATM and Chk1/2, and inactivation of Cdc2 and CDK2 phosphorylation.

New development of laser ion source for highly charged ion beam production at Institute of Modern Physics (invited).

A laser ion source based on Nd:YAG laser has been being studied at the Institute of Modern Physics for the production of high intensity high charge state heavy ion beams in the past ten years, for possible applications both in a future accelerator complex and in heavy ion cancer therapy facilities. Based on the previous results for the production of multiple-charged ions from a wide range of heavy elements with a 3 J/8 ns Nd:YAG laser [Zhao et al., Rev. Sci. Instrum. 85, 02B910 (2014)], higher laser energy and intensity in the focal spot are necessary for the production of highly charged ions from the elements heavier than aluminum. Therefore, the laser ion source was upgraded with a new Nd:YAG laser, the maximum energy of which is 8 J and the pulse duration can be adjusted from 8 to 18 ns. Since then, the charge state distributions of ions from various elements generated by the 8 J Nd:YAG laser were investigated for different experimental conditions, such as laser energy, pulse duration, power density in the focal spot, and incidence angle. It was shown that the incidence angle is one of the most important parameters for the production of highly charged ions. The capability of producing highly charged ions from the elements lighter than silver was demonstrated with the incidence angle of 10° and laser power density of 8 × 10(13) W cm(-2) in the focal spot, which makes a laser ion source complementary to the superconducting electron cyclotron resonance ion source for the future accelerator complex especially in terms of the ion beam production from some refractory elements. Nevertheless, great efforts with regard to the extraction of intense ion beams, modification of the ion beam pulse duration, and reliability of the ion source still need to be made for practical applications.

Interleukin-6 and interleukin-8 in diagnosing neonatal septicemia.

Neonatal septicemia (NS) is a common cause of death of newborn infants, hence early diagnosis and treatment are of the utmost importance. However, lack of specific clinical symptoms and late detection delay a correct diagnosis. It is therefore of great importance to establish auxiliary indexes for the early diagnosis of NS. To evaluate the value of interleukin (IL-6 and IL-8) in the diagnosis of NS, a prospective study was carried out. Seventy-five newborns who developed septicemia and received treatment in our hospital from January 2013 to December 2014 were selected as research subjects; also, 50 healthy newborns were set as a control group. The levels of serum IL-6 and IL-8 were compared between the two groups. Results demonstrated that levels of C-reactive protein (CRP), IL-6 and IL-8 of the septicemia group were higher than those of the control group on admission, although the difference had no statistical significance (P less than 0.05); the septicemia group had higher sequential organ failure assessment (SOFA) scores but lower pediatric critical illness scores (PCIS) compared to the control group (P less than 0.05); levels of CRP, IL-6 and IL-8 were in positive correlation to the SOFA scores and in negative correlation to PCIS. Analysis of receiver operating characteristics (ROC) curve demonstrated that the sensitivity, specificity and accuracy were 85.7%, 80.2% and 81.8%, respectively, when IL-6 level was set as 32 pg/mL, 78.1%, 64.2% and 66.9%, respectively when IL-8 level was set as 54 pg/mL, and 71.4%, 86.3% and 82.7% respectively, when detection of IL-6 and IL-8 were combined together. Hence it can be concluded that: IL-6 and IL-8 are involved in inflammatory reactions; levels of IL-6 and IL-8 were correlated to the severity of the infection; the value of IL-6 is higher than that of IL-8 in the diagnosis of neonatal septicemia and the combined detection of IL-6 and IL-8 can improve the accuracy of the diagnosis of neonatal septicemia.

Simulation of direct plasma injection for laser ion beam acceleration with a radio frequency quadrupole.

The direct plasma injection scheme (DPIS) has been being studied at Institute of Modern Physics since several years ago. A C(6+) beam with peak current of 13 mA, energy of 593 keV/u has been successfully achieved after acceleration with DPIS method. To understand the process of DPIS, some simulations have been done as follows. First, with the total current intensity and the relative yields of different charge states for carbon ions measured at the different distance from the target, the absolute current intensities and time-dependences for different charge states are scaled to the exit of the laser ion source in the DPIS. Then with these derived values as the input parameters, the extraction of carbon beam from the laser ion source to the radio frequency quadrupole with DPIS is simulated, which is well agreed with the experiment results.

EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo.

BACKGROUND: EIF5A2, eukaryotic translation initiation factor 5A2, is associated with several human cancers. In this study, we investigated the role of EIF5A2 in the metastatic potential of localised invasive bladder cancer (BC) and its underlying molecular mechanisms were explored. METHODS: The expression pattern of EIF5A2 in localised invasive BC was determined by immunohistochemistry. In addition, the function of EIF5A2 in BC and its underlying mechanisms were elucidated with a series of in vitro and in vivo assays. RESULTS: Overexpression of EIF5A2 was an independent predictor for poor metastasis-free survival of localised invasive BC patients treated with radical cystectomy. Knockdown of EIF5A2 inhibited BC cell migratory and invasive capacities in vitro and metastatic potential in vivo and reversed epithelial-mesenchymal transition (EMT), whereas overexpression of EIF5A2 promoted BC cells motility and invasiveness in vitro and metastatic potential in vivo and induced EMT. In addition, we found that EIF5A2 might activate TGF-ß1 expression to induce EMT and drive aggressiveness in BC cells. EIF5A2 stabilized STAT3 and stimulated nuclear localisation of STAT3, which resulted in increasing enrichment of STAT3 onto TGF-ß1 promoter to enhance the transcription of TGF-ß1. CONCLUSIONS: EIF5A2 overexpression predicts tumour metastatic potential in patients with localised invasive BC treated with radical cystectomy. Furthermore, EIF5A2 elevated TGF-ß1 expression through STAT3 to induce EMT and promotes aggressiveness in BC.

Laparoscopic excision of a large prostatic utricle revealed by haematuria: 1-year follow-up.

Prostatic utricles revealed by the presentation of haematuria are very rare. Only limited experience with laparoscopic surgery of prostatic utricle has been reported to date. Herein we report a 20-year-old male with frequently terminal haematuria and oligozoospermia who underwent successful laparoscopic excision of a large prostatic utricle. Haematuria disappeared and semen quality improved during 1-year follow-up.

Knockdown of insulin-like growth factor I receptor inhibits the growth and enhances chemo-sensitivity of liver cancer cells.

Liver cancer is one of the most common malignant cancers worldwide. Systemic chemotherapy remains the major treatment option, but with severe adverse effects. Combinations of systemic with targeted treatments may provide effective therapeutics. The objectives of this study were to demonstrate if insulin-like growth factor-I receptor (IGF-IR) might serve as a functional target for liver cancer treatment and to investigate the chemo-sensitizing activity of IGF-IR downregulation. IGF-IR knockdown was achieved by stable transfection of liver cancer cells with IGF-IR small interfering RNA (siRNA). IGF-IR knockdown resulted in reduced growth, clonogenic survival, adhesion and migration of liver cancer cells, and increased sensitivities of liver cancer cells to apoptosis-inducing agents and chemotherapeutic drugs in vitro. In the animal studies, both IGF-IR knockdown and adriamycin (ADM) treatment significantly reduced the growth of liver tumors. IGF-IR knockdown enhanced the effect of ADM on tumor growth by further reducing tumor angiogenesis and inducing tumor cell apoptosis. The final tumor sizes in the IGFIR-siRNA, ADM-treated EGFP, and ADM-treated IGFIR-siRNA groups were significantly reduced by 52.5%, 33.8%, and 86.3%, respectively, compared with that in the EGFP control, suggesting that the ADM and the IGF-IR knockdown inhibit the growth of liver tumors in a synergistic manner. These results support that IGF-IR may serve as a functional molecular target for liver cancer treatment, and that the combination of systemic chemotherapy with targeted IGF-IR suppression may provide an effective treatment strategy for liver cancer.