[Long-term outcome of EVAHEART I implantable ventricular assist device for the treatment of end stage heart failure: clinical 3-year follow-up results of 15 cases].

Objective: To evaluate the long-term efficacy and safety of the implantable ventricular assist system EVAHEART I in clinical use. Methods: Fifteen consecutive patients with end-stage heart failure who received left ventricular assist device therapy in Fuwai Hospital from January 2018 to December 2021 were enrolled in this study, their clinical data were retrospectively analyzed. Cardiac function, liver and kidney function, New York Heart Association (NYHA) classification, 6-minute walk distance and quality of life were evaluated before implantation and at 1, 6, 12, 24 and 36 months after device implantation. Drive cable infection, hemolysis, cerebrovascular events, mechanical failure, abnormally high-power consumption and abnormal pump flow were recorded during follow up. Results: All 15 patients were male, mean average age was (43.0±7.5) years, including 11 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 2 cases of valvular heart disease. All patients were hemodynamically stable on more than one intravenous vasoactive drugs, and 3 patients were supported by preoperative intra aortic balloon pump (IABP). Compared with before device implantation, left ventricular end-diastolic dimension (LVEDD) was significantly decreased ((80.93±6.69) mm vs. (63.73±6.31) mm, P<0.05), brain natriuretic peptide (BNP), total bilirubin and creatinine were also significantly decreased ((3 544.85±1 723.77) ng/L vs. (770.80±406.39) ng/L; (21.28±10.51) µmol/L vs. (17.39±7.68) µmol/L; (95.82±34.88) µmol/L vs. (77.32±43.81) µmol/L; P<0.05) at 1 week after device implantation. All patients in this group were in NYHA class Ⅳ before implantation, and 9 patients could recover to NYHA class Ⅲ, 3 to class Ⅱ, and 3 to class Ⅰ at 1 month after operation. All patients recovered to class Ⅰ-Ⅱ at 6 months after operation. The 6-minute walk distance, total quality of life and visual analogue scale were significantly increased and improved at 1 month after implantation compared with those before operation (P<0.05). All patients were implanted with EVAHEART I at speeds between 1 700-1 950 rpm, flow rates between 3.2-4.5 L/min, power consumption of 3-9 W. The 1-year, 2-year, and 3-year survival rates were 100%, 87%, and 80%, respectively. Three patients died of multiple organ failure at 412, 610, and 872 d after surgery, respectively. During long-term device carrying, 3 patients developed drive cable infection on 170, 220, and 475 d after surgery, respectively, and were cured by dressing change. One patient underwent heart transplantation at 155 d after surgery due to bacteremia. Three patients developed transient ischemic attack and 1 patient developed hemorrhagic stroke events, all cured without sequelae. Conclusion: EVAHEART I implantable left heart assist system can effectively treat critically ill patients with end-stage heart failure, can be carried for long-term life and significantly improve the survival rate, with clear clinical efficacy.

Regenerating gene IA predicts radiosensitivity and survival in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. Radiotherapy is the main treatment option. However, radiotherapy does not benefit all patients because there is no known precise biomarker that can be used for screening radioresistant patients. Genetic predisposition is closely related to tumor development, therapeutic response, and prognosis. The relationship between regenerating gene IA (REGIA) and NPC is unclear. This study aimed to retrospectively analyze the association between REGIA expression and metastasis, radiosensitivity, and survival in patients with NPC as well as assess the effect of radiation on REGIA expression in vitro. Immunohistochemical staining was used to detect REGIA. The relationship between REGIA expression in radioresistant NPC and the prognosis of CNE1 NPC cells were analyzed using quantitative real-time polymerase chain reaction and Western blotting. We found that increased doses of radiation in CNE1 cells significantly decreased REGIA expression (P<0.05). The overall rate of REGIA-positive expression was 47.15% in NPC tissues and 45.00% and 61.02% in radiosensitive and radioresistant cases, respectively, showing significant differences (P<0.05). A REGIA-positive protein expression rate had a negative correlation with radiosensitivity in NPC (r= -0.109, P=0.047). Both REGIA-positive and REGIA-negative expression strongly predicted the overall survival rate and progression-free survival of NPC patients (P<0.01). A multivariate analysis indicated that REGIA was an inverse prognostic factor in NPC patients (REGIA-positive expression: hazard ratio (HR)=2.139, 95% confidence interval (CI)=1.56-2.94, P<0.001 and REGIA-negative expression: HR=1.958, 95% CI=1.42-2.69, P<0.001). In conclusion: Radiation can affect REGIA expression. The REGIA expression level correlated with radioresistance and a poor prognosis. In addition, REGIA expression might act as a potential therapeutic target and prognostic predictor in NPC patients.

Invasive pulmonary fungal infections in children with severe human adenovirus type 7 pneumonia: A retrospective study.

BACKGROUND: There has been a rapid increase in the number of human adenovirus type 7 (HAdV-7) and invasive pulmonary fungal infections (IPFIs) co-infection. METHODS: In this study, we included patients with confirmed HAdV-7 infection during the period from 2018 to 2019 to explore clinical characteristics of severe HAdV-7 pneumonia combined with IPFIs. RESULTS: Among the 143 patients, 35 cases were co-infected with IPFIs. Others were assigned to the control group (n Z 108). Patients wereprone to be complicated with respiratory failure, heart failure and hemophagocytic syndromein IPFIs group. Thirty-one species of fungi were detected in the IPFIs group, among whichAspergillus was the most common species. Compared to control group, patients had lowerlevels of WBC, CD3þ T lymphocyte counts and CD19þ B lymphocyte counts in IPFIs group. CONCLUSION: Aspergillus is the most common species in IPFIs combined with severe HAdV-7 pneumonia. For children with severe HAdV-7 pneumonia who are younger, have a long course of disease, and have been admitted to the ICU, we should predict the occurrence of IPFIs when there is multi-system dysfunction and the reduction of CD3+ T lymphocyte counts and CD19+ B lymphocyte counts in course of their disease.

[Establishment and validation of prognosis predictive model using m6A RNA methylation regulators in children acute myeloid leukemia].

Objective: To figure out the association between the expression of m6A RNA methylation regulators and the prognosis of children AML, and provide genetic markers for monitoring the progression and recurrence of AML. Methods: Twenty two m6A RNA methylation regulators were firstly analyzed using the data from Therapeutically Applicable Research To Generate Effective Treatments(TARGET) database and The Genotype-Tissue Expression(GTEx) database, Wilcoxon rank test was performed to analyze the differentially expression of m6A RNA methylation regulators between the AML and normal tissue, 296 AML children were divided into training cohort and validation cohort by simple random sampling method, Lasso regression was used to screen out the risk factors and the multivariate Cox regression was applied for establishing prognosis predicting model in training cohort. Kaplan-Meier survival curve, time-dependent ROC curve and multivariate Cox regression were used to estimate the efficiency of risk score calculated by predictive model in validation cohort. Results: Twenty one m6A genes were up regulated in AML compared to Normal patients. Five m6A RNA methylation regulators(ZC3H13, YTHDC2, HNRNPA2B1, METTL3, METTL5) were included in final predicting model. Risk score could independently predict the survival of AML patients in training cohort(HR:2.72, 95%CI: 1.54-4.81, P=0.000 6) and validation cohort(HR:2.01, 95%CI:1.14-3.50, P=0.016). Low-risk patients had better prognoses than high-risk patients both in training cohort(P=0.001 9) and validation cohort(P=0.023). Conclusion: This prognosis predicting model constructed by m6A RNA methylation regulators could independently predict the survival prognosis in AML children, and should be helpful for clinical therapy.

[Consistency of peripheral whole blood and venous serum procalcitonin in children: a multicenter parallel controlled study].

Objective: To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection. Methods: This multicenter cross-sectional parallel control study was conducted in 11 children's hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman's rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection. Results: A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum (r=0.97, P<0.01). The linear regression equation was PCTvenous serum=0.135+0.929×PCTperipheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods (r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 µg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 µg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 µg/L, respectively. Conclusions: There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.

[Misdiagnosis analysis: 120 patients with nasal extranodal NK/T cell lymphoma in head and neck].

Objective:The Clinicopathological characteristics and the reason of misdiagnosis about nasal extranodal NK/T cell lymphoma in head and neck（ENKTL） are analysised to raise awareness and reduce misdiagnosis. Method:One hundred and twenty patients with ENKTL, diagnosed pathologically in head and neck from May 2010 to April 2018, were analyzed retrospectively. All cases were divided into misdiagnosed group and non-misdiagnosed group according to whether there were misdiagnosis and mistreatment before diagnosis. The differences of clinicopathological characteristics between the two groups before and after diagnosis were compared. The differences of overall survival（OS） between the two groups after treatment were also compared. Result:The misdiagnosis rate of this study was 71.7%, and they were misdiagnosed as sinusitis, nasal polyps, upper respiratory tract infection and so on. On the whole, the 1-year OS, 3-year OS and 5-year OS were 77.8%, 65.9% and 49.3% respectively. There was no significant difference in sex, age, first symptom, initial site, B symptom, superficial lymph node enlargement and weight loss between two groups before diagnosis（P>0.05）, however, there were significant differences in relative specific signs, hospital grade and time from first visit to definite diagnosis（P<0.05）. The proportion of the high-level hospitals in the first visit hospital was significantly lower than that in the non-misdiagnosed group, while the time from the first visit to the final diagnosis was significantly longer than that in the non-misdiagnosed group. There was no significant difference in international prognostic index（IPI） score, expression of Ki-67, therapeutic schedule, chemotherapy regimen for patients receiving chemotherapy, and radiation dose for patients receiving radiotherapy after diagnosis between the two groups（P>0.05）, but there was a significant difference in the clinical stages of Ann Arbor between the two groups（P<0.05）. The clinical staging of the misdiagnosed group was later than that of the non-misdiagnosed group. The 1-year OS, 3-year OS and 5-year OS were 73.6%, 59.3% and 43.2% in the misdiagnosed group respectively, and 88.2%, 82.4% and 64.2% in the non-misdiagnosed group respectively. The overall survival rate in the misdiagnosis group was lower than that in the non-misdiagnosed group, and the overall survival time was lower than that in the non-misdiagnosed group. However, there was no significant difference in the overall survival rates between the early stage（Ⅰ and Ⅱ） and the advanced stage（Ⅲ and Ⅳ） of Ann Arbor（P>0.05）. Conclusion:The non-specific clinical and the complexity of pathological features of ENKTL in head and neck might cause misdiagnosis, which leads to prolonged time from first visit to definite diagnosis, thus results in disease progression, and ultimately may lead to decreased overall survival rate. To avoid the misdiagnosis and early diagnosis is very important.

[Therapeutic effect of low-temperature radiofrequency coblation on early-stage laryngeal cancer].

Objective: To evaluate the safety,efficacy and prognosis of low-temperature plasma radiofrequency coblation for early-stage laryngeal cancer(Tis, T1 and T2). Method: A retrospective analysis of 202 patients with early-stage laryngeal cancer who underwent the low-temperature radiofrequency coblation surgery, including 34 cases of Tis(16.83%), 49 cases of stage T1aN0M0(24.26%), 50 cases of stage T1bN0M0(24.75%) and 69 cases of stage T2N0M0(34.16%). Surgical patients were followed up closely for 6 to 60 months, with a median follow-up of 29 months. Result: Of the 202 patients,165(81.68%) had no recurrence and achieved good surgical results. None of them suffered severe complications such as post-operative hemorrhage and asphyxia. 37 cases(18.32%) had recurrence, including 1 case(0.50%) in stage Tis, 7 cases(3.47%) in stage T1a,7 cases(3.47%) in stage T1b, and 22 cases(10.89%) in stage T2. Thirteen patients who had recurrence underwent total laryngectomy(5 of which had a recurrence of T3 and 8 of which progressed to T4), including 1 in the stage T1a,2 in the stage T1b, and 10 in the stage T2. Vertical hemilaryngectomy were performed in 4 cases, 3 cases of stage T1a and 1 case of stage T2; 5 cases underwent plasma radiofrequency coblation again, including 3 cases of stage T1b and 2 cases of stage T2,no recurrence was found in all the patients; 1 patient had no obvious recurrence in the larynx but had cervical lymph node metastasis, radical neck dissection was performed; 1 patient with stage T2 recurrence was treated with a tracheotomy to relieve laryngeal obstruction without further treatment;3 cases showed improvement by radiotherapy and chemotherapy treatment after recurrence; 9 death cases,5 patients died after radiotherapy and chemotherapy, and 4 patients stopped getting treatment after recurrence.Conclusion: Low-temperature radiofrequency coblation surgery for patients with early-stage laryngeal cancer has great advantages in the preservation of laryngeal function and reduction of surgical trauma after surgery compared with traditional surgical method, and can obtain satisfactory results, but the selection of surgical indications for some patients with clinical stage T2 is still need to be carefully considered..

MicroRNA-200c represses migration and invasion of gastric cancer SGC-7901 cells by inhibiting expression of fibronectin 1.

OBJECTIVE: Gastric cancer remains a worldwide burden as a leading cause of cancer-related death. Drug resistance of chemotherapy looms as a major clinical challenge to effective treatment. Recent research data has suggested that microRNAs could be a potential gastric cancer treatment strategy. To further evaluate the role of microRNAs on gastric cancer cells and its underlying possible mechanism, we transfected human gastric cancer SGC-7901 cells with microRNA-200c. MATERIALS AND METHODS: The cell proliferation, migration and invasion of SGC-7901 were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Transwell assay and cell invasion assay. The expression of FN1 was detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) assay. RESULTS: The cell proliferation, migration and invasion were all significantly decreased after microRNA-200c transfection. Moreover, Fibronectin 1 (FN1) expression was significantly inhibited by microRNA-200c transfection. These results indicated that the mechanism by which microRNA-200c impresses human gastric cancer SGC-7901 cells may be mediated by its inhibition on FN1 expression. CONCLUSIONS: This study highlighted the potential of using microRNA-200c as a new treatment strategy for human gastric cancer.

Serum soluble RAGE level inversely correlates with left ventricular hypertrophy in essential hypertension patients.

Soluble receptor for advanced glycation end-products (sRAGE) acts as a decoy to prevent interaction between RAGE and its pro-inflammatory ligands. sRAGE levels have been found to decrease in chronic inflammatory diseases, including hypertension. However, few data have been reported concerning the association between serum sRAGE levels and hypertensive left ventricular hypertrophy (LVH). Fasting blood samples were obtained from 209 essential hypertensive patients, and sRAGE levels were measured using a commercially available double-sandwich enzyme-linked immunosorbent assay kit. All patients underwent complete transthoracic echocardiographic examination. LVH was defined as a left ventricular mass index >115 g/m(2) for men and >95 g/m(2) for women. Eighty-one hypertensive patients (38.76%) were categorized in the LVH(+) group. Age (P = 0.009), hypertension duration (P = 0.013), triglyceride levels (P = 0.028), and systolic blood pressure (P = 0.026) were higher, and sRAGE and high-density lipoprotein cholesterol levels were lower in the LVH(+) group compared with the LVH(-) group. Multivariate logistic regression analysis showed that sRAGE level [odds ratio (OR) = 0.916; 95% confidence interval (CI) = 0.864-0.984; P = 0.003], hypertension duration (OR = 1.024; 95%CI = 1.003-1.052; P = 0.027), and triglyceride level (OR = 1.017; 95%CI = 1.005-1.039; P = 0.018) were independent predictors of LVH in hypertensive patients. In conclusion, serum sRAGE level was inversely associated with LVH in hypertensive patients.

Cancer stem cell targets - a review.

The varied therapeutic approaches like radiotherapy, chemotherapy, surgery, etc. primarily aimed to target cancer cells specifically. Despite these efforts, they are not completely successful in eliminating this deadly pathological state. These failures ultimately lead to cancer reoccurrence, which is again, another burning problem associated with cancer. The prime reason for the above observation has been found to be the development of resistance by cancer cells towards cancer drugs or cancer-initiating cells (cancer stem cells) remain unaffected by existing treatment procedures. Recent research has evolved two drugs, salinomycin and apoptin, that hold great potential for the future of cancer treatment not only for restricting malignancy, but also in preventing tumor recurrence. The present review article will put light on these new upcoming cancer stem cell targeting agents.

Construction of an anthropopathic abdominal phantom for accuracy validation of deformable image registration.

The purpose of this study is to design and fabricate an anthropopathic abdominal phantom for accuracy evaluation of deformable image registration (DIR) algorithms in adaptive radiation therapy. The constructed deformable organs, including the liver, kidney, spleen and stomach, are made of mixture of polyvinyl chloride (PVC) and softener dioctyl terephthalate, while the rigid structures, i.e. vertebrae, are made of white cement. Relation between the PVC-softener blending ratio and organ CT number is studied, and three-dimensional printing technic is employed to create highly anthropopathic organs in terms of organ shape and density. Detailed steps for phantom construction, landmark point placement and choice of phantom ingredients and construction recipe are introduced. Preliminary results of the mechanical properties of the fabricated organs are also presented. The experimental results indicate that the constructed phantom has satisfactory elastic characteristics and close CT number with corporal organs, and can potentially be applied to simulate real abdominal organ deformation in geometric accuracy validation of DIR algorithms.

[The clinical and imaging features of 118 patients with spontaneous cerebral arterial dissections presenting with ischemic stroke].

OBJECTIVE: To investigate the clinical and radiologic features of patients with spontaneous cerebral arterial dissections (CADs) presenting with ischemic stroke and to explore the effect of gender and age on those features. METHODS: Patients admitted to our stroke center diagnosed as ischemic stroke secondary to CADs from August 2008 to April 2015 were prospectively registered. Patients aged between 15 to 80 years old, who had acute brain infarcts within the territory of a major cerebral artery affected by a dissection confirmed by the neuroradiological examinations, were enrolled in the study. The followings were the exclusion criteria: (1) there were any potential causes for the brain infarcts other than CADs; (2) CADs were the results of a definite cause; (3) the clinical data were incomplete. RESULTS: A total of 118 patients were enrolled in the study with the mean age of (44.2±12.8) years old. There were 87 men (73.7%) and 67 patients (56.8%) aged under 45 years old. Smoking (41.5%), hypertension (25.4%) and hypercholesterolemia (21.2%) were the three leading risk factors for stroke. Hypercholesterolemia was more common in the male patients (25.3% vs 9.7%, P=0.021), whereas hypertension (39.2% vs 14.9%, P=0.005) and diabetes (25.5% vs 4.5%, P=0.002) were more common in the patients aged 45 years or older. Headache or neck pain before or at the onset of stroke was more common in the female patients (67.7% vs 34.5%, P=0.002). A total of 71 patients were found with CADs of the anterior circulation, while 47 patients with that of the posterior circulation. The involvement of the intra and extracranial arteries were documented in 59 and 59 patients, respectively. The middle cerebral artery (MCA) was the most common site in the intracranial dissection and more MCA dissections were observed in the male patients (46.3% vs 11.1%, P=0.016). The dissection of intracranial carotid artery was more common in patients aged under 45 years old (38.7% vs 0, P<0.001). Lumen status of CADs often presented as stenosis (43.2%) and occlusion (41.2%), while less aneurysm (5.9%) and aneurysm with stenosis (9.3%) were observed. Aneurysm was found to be more common in patients aged 45 years or older (11.8% vs 1.5%, P=0.042). CONCLUSION: Chinese patients with spontaneous CADs presenting with ischemic stroke have unique clinical and imaging features, which correlated with age and gender.

Hypoxic markers in non-small cell lung cancer (NSCLC) - A review.

Surgery, chemotherapy and radiotherapy have been the main pillars of cancer treatment. Some of the recent improvements in survival of other cancers can be attributed to novel treatment therapies. Such therapies mostly target specific molecules involved in cancer progression and metastasis. Development and clinical introduction of targeted therapies involve identification of new and potentially important molecules in cancer progression. The next important step is to evaluate its prognostic value. Prognostication by molecular markers is also important as this may identify subgroups of patients in need for additional treatment or not, which was not possible with the traditional clinic-pathological prognosticators. Hypoxic markers have been widely explored in the recent past for their prognostic efficacy in non-small cell lung cancer. The present review article will enlighten importance of hypoxic markers with special reference to non-small cell lung carcinoma.

Confirmation of soybean plastid rRNAs by formaldehyde denaturing agarose gel electrophoresis.

Owing to their prokaryotic origin, plastid rRNAs are mainly 23s/16s/5s rRNAs. We present a novel plant RNA isolation method in this paper. Also, not only the eukaryotic 28s (26s, 25s)/18s rRNAs but the prokaryotic 26s/23s rRNAs as well were demonstrated in a single sample for the first time by formaldehyde denaturing agarose gel electrophoresis.

A generic plant RNA isolation method suitable for RNA-Seq and suppression subtractive hybridization.

A recently developed revolutionary approach to transcriptomics, RNA-Seq, and suppression subtractive hybridization are powerful tools for gene expression research. However, currently, the difficulty of isolating high-quality RNAs from plant tissues bearing abundant complex polysaccharides, polyphenolics, and secondary metabolites is a serious problem that not only limits the application of these technologies but also hinders studies dealing with RNA in general. We have developed a consistent protocol to prepare highly intact and pure RNAs from tissues of a variety of field-grown plant species, with high yields, in 2 to 3 h. Additionally, this method can be readily applied to mammalian, yeast, and bacterial cells.

Re-analysis of expression profiles for revealing new potential candidate genes of heart failure.

BACKGROUND: Chronic heart failure (HF) is characterized by diminished cardiac output and pooling of blood in the venous system. AIM: We used the GSE1145 microarray data to identify potential genes that related to heart failure to construct a regulation network. MATERIALS AND METHODS: In the network, some of transcription factors (TFs) and target genes have been proved to be related to heart failure in previous study. The gene MYC, RELA, HIF1A, NFκB1 and SMAD3 are as hub nodes in our transcriptional network and have a close relationship with heart failure. RESULTS: The study did not address regulation network but researched for the significant pathways related to chronic heart failure. Besides, RELA and NFκB1 interfere with each other in response to HF. CONCLUSIONS: It is demonstrated that transcriptional network analysis is useful in identification of the candidate genes in heart failure.

Generating ultrabroadband terahertz radiation based on the under-compression mode of velocity bunching.

We propose and analyze a scheme to generate enhanced ultrabroadband terahertz (THz) radiation through coherent transition radiation emitted by ultrashort electron beams based on a 10.5 m beamline at Tsinghua University. The proposed scheme involves the initial compression of the electron beam with a few hundred pC charges using a velocity bunching scheme (i.e., RF compression) in an under-compression mode instead of the usual critical-compression mode in order to maintain a positive energy chirp at the exit of the traveling wave accelerator. After a long drift segment, the particles in the tail catch up with the bunch head. More than 80% of the particles are distributed in a spike with an rms length less than 20 fs. Such beams correspond to an ultrabroadband coherent transition radiation (CTR) spectrum of 0.1 THz to 25 THz, with the single-pulse THz radiation energy of up to 50 µJ. The principle of CTR and under-compression mode of velocity bunching are introduced in this paper. And the ASTRA simulation parameters and the stability of the system are also discussed.

ARRDC3 suppresses breast cancer progression by negatively regulating integrin beta4.

Large-scale genetic analyses of human tumor samples have been used to identify novel oncogenes, tumor suppressors and prognostic factors, but the functions and molecular interactions of many individual genes have not been determined. In this study we examined the cellular effects and molecular mechanism of the arrestin family member, ARRDC3, a gene preferentially lost in a subset of breast cancers. Oncomine data revealed that the expression of ARRDC3 decreases with tumor grade, metastases and recurrences. ARRDC3 overexpression represses cancer cell proliferation, migration, invasion, growth in soft agar and in vivo tumorigenicity, whereas downregulation of ARRCD3 has the opposite effects. Mechanistic studies showed that ARRDC3 functions in a novel regulatory pathway that controls the cell surface adhesion molecule, beta-4 integrin (ITGbeta4), a protein associated with aggressive tumor behavior. Our data indicates ARRDC3 directly binds to a phosphorylated form of ITGbeta4 leading to its internalization, ubiquitination and ultimate degradation. The results identify the ARRCD3-ITGbeta4 pathway as a new therapeutic target in breast cancer and show the importance of connecting genetic arrays with mechanistic studies in the search for new treatments.

Altered expression of estrogen receptor alpha and beta in advanced gastric adenocarcinoma: correlation with prothymosin alpha and clinicopathological parameters.

AIMS: We aimed to investigate the sources of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and estimate the value of both ER subtypes in gastric adenocarcinoma and analyze the possible relationship of prothymosin alpha (ProTalpha) to ERs. METHODS: ERs at the mRNA and protein levels in matched advanced gastric adenocarcinomas and surrounding non-cancerous tissues were examined by using reverse transcription-polymerase chain reaction and immunohistochemical (IHC) methods. Cell proliferation related protein ProTalpha was also detected in IHC. The immunoreactive signal, corresponding to the proteins expression level, was quantitatively analyzed. RESULTS: Both ERalpha and ERbeta mRNAs were detected in most of the cancer and matched normal tissues analyzed. At the protein level, the percentage of ERalpha and ERbeta positive cases changed. ERalpha immunoreactivity was only detected in poorly differentiated adenocarcinoma and ERalpha positive expression correlated with depth of invasion of the tumors. Compared with non-cancerous tissues, gastric tumors showed decreased ERbeta expression and lost ERbeta. Altered ERbeta in gastric adenocarcinoma correlated with decreased differentiation. And the tumors involved lymph node metastasis showed significantly lower expression level of ERbeta. ProTalpha in ERbeta-positive tumors showed higher expression than that in lost ERbeta tumors. CONCLUSIONS: Altered expression of ERalpha and ERbeta in tumors compared with corresponding normal gastric tissues was more common in poorly differentiated adenocarcinomas and related to malignant properties, such as lymph node metastasis. Decreased ERbeta and increased ProTalpha expression in advanced gastric adenocarcinoma indicated that ERbeta may play an anti-proliferation role which is opposed to the role of ProTalpha in gastric epithelium.

Properties of hybrid enzymes between Synechococcus large subunits and higher plant small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase in Escherichia coli.

To explore the function of small subunits of Rubisco, three hybrid enzymes were synthesized in Escherichia coli by construction of a transcriptionally coupled expression system in which the synthetic small subunit gene of rice, tobacco, and wheat, respectively, was cloned downstream from the large subunit gene of Synechococcus sp. PCC6301. These coexpression products were detected by utilizing SDS-PAGE and confirmed by immunoblotting. The amount of carboxylase activity from the intact cells revealed that each higher plant small subunit was able to assemble with the Synechococcus large subunit octamer core to form an active heterologous enzyme in E. coli. However, in these heterologous enzymes, the interaction between large subunits and small subunits was very weak, the small subunit readily dissociated from the large subunit octamer core. A detailed kinetic assay was carried out with the partially purified hybrid enzymes. Compared to Synechococcus Rubisco, the activity of rice, tobacco, and wheat hybrid Rubisco decreased to 37, 61, and 37% of the original activity, respectively. These hybrid enzymes showed a greater affinity for CO2 and RuBP than Synechococcus Rubisco. The specificity factor of the three hybrid Rubiscos was 98, 84, and 76%, respectively, of the original. These results indicate for the first time that the small subunit contributes to the stability, catalytic efficiency, and CO2/O2 specificity of Rubisco together, which suggests that small subunits may be fruitful targets for engineering an improved Rubisco. Meanwhile, we found that sorbitol in the culture of induced cells promoted the production of active assembled enzyme and shortened the time to reach maximal expression.