[RHPN2 is highly expressed in osteosarcoma cells to promote cell proliferation and migration and inhibit apoptosis].

OBJECTIVE: To screen for aberrantly expressed genes in osteosarcoma cells and investigate the role of RHPN2 in regulating the proliferation, apoptosis, migration and tumorigenic abilities of osteosarcoma cells. METHODS: We used GEO2R to analyze the differential gene expression profile between osteosarcoma cells and normal cells in the GSE70414 dataset. RTqPCR and Western blotting were performed to detect RHPN2 expression in osteosarcoma cell lines MG-63, 143B and SAOS2. Two RHPN2-shRNA and a control NC-shRNA were designed to silence the expression of RHPN2 in 143B cells, and CCK8 assay, colony-forming assay, annexin V-FITC/PI staining and scratch assays were carried out to examine the changes in proliferation, apoptosis and migration of the cells. We also established nude mouse models bearing osteosarcoma xenografts derived 143B cells and RHPN2-shRNA-transfected 143B cells, and assessed the effect of RHPN2 silencing on osteosarcoma cell tumorigenesis using HE staining. Kaplan-Meier survival curves were used to analyze the correlation between RHPN2 expression and survival outcomes of patients with osteosarcoma. RESULTS: RHPN2 expression was significantly upregulated in osteosarcoma cell lines MG-63, 143B and SAOS2 (P < 0.01). Silencing of RHPN2 significantly inhibited the proliferation and migration of 143B cells in vitro, promoted cell apoptosis (P < 0.01), and suppressed tumorigenic capacity of the cells in nude mice. A high expression of RHPN2 was significantly correlated with a poor prognosis of patients with osteosarcoma (P < 0.05). CONCLUSION: RHPN2 is highly expressed in osteosarcoma cells to promote cell proliferation and migration and inhibits cell apoptosis. A high expression of RHPN2 is associated with a poorer prognosis of the patients with osteosarcoma.

Experimental Evidence of Intrinsic Current Generation by Turbulence in Stationary Tokamak Plasmas.

High-ß_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-ß_{θe} regime.

Promising High-Confinement Regime for Steady-State Fusion.

A reproducible stationary high-confinement regime with small "edge-localized modes" (ELMs) has been achieved recently in the Experimental Advanced Superconducting Tokamak, which has a metal wall and low plasma rotation as projected for a fusion reactor. We have uncovered that this small ELM regime is enabled by a wide edge transport barrier (pedestal) with a low density gradient and a high density ratio between the pedestal foot and top. Nonlinear simulations reveal, for the first time, that the underlying mechanism for the observed small ELM crashes is the upper movement of the peeling boundary induced by an initial radially localized collapse in the pedestal, which stops the growth of instabilities and further collapse of the pedestal, thus providing a physics basis for mitigating ELMs in future steady-state fusion reactors.

Influence of neutral beam attenuation on beam emission spectroscopy and charge exchange recombination spectroscopy.

Neutral beam attenuation is simulated by means of consulting the ADAS (Atomic Data and Analysis Structure) database based on experimentally diagnosed radial plasma density and electron temperature profiles on the Experimental Advanced Superconducting Tokamak (EAST). Two-dimensional distributions of beam emission and charge exchange recombination photon flux are simulated, taking neutral beam attenuation into account, together with comparison with experimental results of Beam Emission Spectroscopy (BES) and Charge eXchange Recombination Spectroscopy (CXRS). A photon number which is over 1014 promises a sufficient photon flux for typical detectors of BES, CXRS, and UltraFast-CXRS (UF-CXRS) diagnostics. Evidence shows that the ADAS database overvalues neutral beam injection effective stopping coefficient on the EAST tokamak. The joint diagnostic of BES and UF-CXRS which is under development to measure plasma pressure with a high temporal resolution of 1 µs will have strong signals in a radial range of 0.6 < ρ < 0.8. The steep gradients of plasma density and C6+ density at ρ ∼ 1 bring great difficulty to edge plasma investigation by this joint diagnostic.

Enhanced expression of non coding miR 92a expression is implicated in the development of lung cancer.

OBJECTIVE: MicroRNAs (miRNAs/miRs) are small noncoding RNAs that primarily function in RNA silencing and gene regulation at the posttranscriptional level in animals, plants and certain viruses. They have been reported to play a vital role in development and progression of diseases such as cancer. The present study was undertaken to establish a correlation between a specific miRNA in this cluster, termed miR92a, and its association with nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Total RNA was isolated from the plasma using an RNeasy mini kit and cDNA was synthesized by TaqMan MicroRNA Reverse Transcription kit. The expression of miR-92a was quantified by quantitative Real-time PCR (RT-PCR). All transfections were performed using Lipofectamine 2000. Digoxigenin (DIG)labeled locked nucleic acid (LNA)modified probes for miR92a and negative control oligonucleotides were used for in vitro hybridization following manufacturers protocol. Digoxigenin (DIG)labeled locked nucleic acid (LNA)modified probes for miR92a and negative control oligonucleotides (miRCURY LNA MicroRNA Detection Probes; Exiqon, Vedbaek, Denmark) were used. Cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. RESULTS: It was observed that miR92a is highly expressed in NSCLC compared with adjacent tissue samples and plasma from healthy donors. Additionally, the proliferation of three NSCLCderived cell lines, SPCA1, A549 and H2170, was enhanced by miR92a and inhibited by a complementary antimiR92a oligonucleotide sequence. Although the underlying mechanisms of reduced cellular proliferation in the presence of miR92a antagomirs cannot be explained from the current results. CONCLUSIONS: The upregulation of miR92a expression, in cells and plasma, is manifested during the development of NSCLC.

WITHDRAWN: Expression and clinicopathological significance of Mel-18 and Bmi-1 in oesophageal squamous cell carcinoma.

This article has been withdrawn at the request authors.

Validation of fast-ion D-alpha spectrum measurements during EAST neutral-beam heated plasmas.

To investigate the fast ion behavior, a fast ion D-alpha (FIDA) diagnostic system has been installed on EAST. Fast ion features can be inferred from the Doppler shifted spectrum of Balmer-alpha light from energetic hydrogenic atoms. This paper will focus on the validation of FIDA measurements performed using MHD-quiescent discharges in 2015 campaign. Two codes have been applied to calculate the Dα spectrum: one is a Monte Carlo code, Fortran 90 version FIDASIM, and the other is an analytical code, Simulation of Spectra (SOS). The predicted SOS fast-ion spectrum agrees well with the measurement; however, the level of fast-ion part from FIDASIM is lower. The discrepancy is possibly due to the difference between FIDASIM and SOS velocity distribution function. The details will be presented in the paper to primarily address comparisons of predicted and observed spectrum shapes/amplitudes.

Nonlinear Transition from Mitigation to Suppression of the Edge Localized Mode with Resonant Magnetic Perturbations in the EAST Tokamak.

Evidence of a nonlinear transition from mitigation to suppression of the edge localized mode (ELM) by using resonant magnetic perturbations (RMPs) in the EAST tokamak is presented. This is the first demonstration of ELM suppression with RMPs in slowly rotating plasmas with dominant radio-frequency wave heating. Changes of edge magnetic topology after the transition are indicated by a gradual phase shift in the plasma response field from a linear magneto hydro dynamics modeling result to a vacuum one and a sudden increase of three-dimensional particle flux to the divertor. The transition threshold depends on the spectrum of RMPs and plasma rotation as well as perturbation amplitude. This means that edge topological changes resulting from nonlinear plasma response plays a key role in the suppression of ELM with RMPs.

Misdiagnosis of an α-fetoprotein-producing esophageal carcinoma: A case report and literature review.

α-fetoprotein (AFP)-producing esophageal carcinoma is a rare type of esophageal cancer, with its characteristics not yet fully clarified. In the present study, a case of esophageal carcinoma was misdiagnosed as an AFP-producing esophageal carcinoma. The patient was a 50-year-old woman who was referred to Qianfoshan Hospital Affiliated to Shandong University in November 2014 with a 3-month history of progressive dysphagia. A chest computed tomography (CT) scan showed thickening of the wall of the esophagus, corresponding regions of luminal stenosis and massive lymph node swelling around the lesser curvature of the esophagus. A laboratory investigation showed that the serum AFP levels of the patient were elevated to 18.97 ng/ml (normal range <12 ng/ml). These laboratory investigation findings combined with the aforementioned pathological diagnosis supported a diagnosis of AFP-producing esophageal carcinoma. An abdominal ultrasound was performed and a cystic low-density measuring 5×4 mm was identified. No metastases were revealed in the liver. The boundary of the focal low density was clear, which indicated a clinical diagnosis of liver cyst. A radical esophagectomy was performed on December 5, 2014. Microscopically, the tumor was a moderately differentiated squamous cell carcinoma invading the serous layer, with no hepatoid features. Immunohistochemistry showed that the cells were diffusely negative for AFP expression. Histopathological examination revealed the absence of hepatoid features. According to these findings, the tumor was diagnosed as a moderately differentiated squamous cell carcinoma. In the present study, the case of a patient with squamous cell carcinoma that was misdiagnosed as an α-fetoprotein-producing esophageal carcinoma was reported, with a review of the literature.

α-fetoprotein-producing gastric carcinoma: A case report of a rare subtype and literature review.

α-fetoprotein (AFP)-producing gastric carcinoma is a rare type of gastric cancer, and the characteristics have not yet been fully elucidated. The present study reports the case of a patient with this type of gastric cancer. A 66-year-old male was referred to the Department of Gastrointestinal Surgery, Qianfoshan Hospital, Shandong University (Jinan, China) with a 20-day history of retrosternal pain. A computed tomography (CT) scan revealed a thickening of the wall of the cardia and massive lymph node swelling in the region of the lesser curvature of the stomach. A laboratory investigation revealed that the serum AFP levels of the patient were elevated to 46.49 ng/ml (normal level, <12.00 ng/ml), and the serum carcinoembryonic antigen (CEA) levels were 382.22 ng/ml (normal range, <5.00 ng/ml). An endoscopy revealed an elevated tumor and AFP-producing gastric cancer was diagnosed. As the tumor was surgically unresectable, the patient received systemic adjuvant chemotherapy [consisting of 1 cycle of oxaliplatin (150 mg; day 1)-fluorouracil(1.0 g; days 2-6)-calcium folinate (0.3 g; days 2-6), 4 cycles of paclitaxel (80 mg; day 1 and 8, repeated day 21) and capecitabine (1,000 g/m2, twice daily; days 1-14, repeated day 21), and 2 cycles of oxaliplatin (130 mg/m2; day 1, repeated day 21) and S-1 (100 mg/d; day 1- day 14; repeated day 21)]. During the chemotherapy intermission, the patient experienced partial remission; the serum AFP levels remained between 44.5 and 32.7 ng/ml, and serum CEA levels decreased to a normal level. The CT scan revealed that the enlarged lymph nodes of the patient had decreased in size. During the preoperative examinations, an abdominal CT scan revealed no metastasis to the liver. A radical gastrectomy was performed on October 20, 2014. Additionally, the tumor did not demonstrate the diffusion of AFP. The histopathological examination revealed a poorly differentiated adenocarcinoma, with local and neuroendocrine differentiation and no hepatoid features. According to these histopathological findings, the tumor was diagnosed as AFP-producing non-hepatoid adenocarcinoma of the stomach. The patient was treated with systemic immunity-enhancing therapy and has been free of recurrence for 2 months. The present study describes a rare case of AFP-producing non-hepatoid adenocarcinoma of the stomach, with a review of the literature and an investigation of the clinical features.

Synchronous double primary cancer of the lung and nasal vestibule: A case report and literature review.

Squamous cell carcinoma (SCC) of the nasal vestibule is a rare tumor entity, and its occurrence combined with lung cancer is even rarer. Thus, several patients are often initially misdiagnosed or remain undiagnosed. This is the case report of a 55-year-old male patient who presented to our hospital with a neoplasm in the left lung. The patient was treated with left upper pulmonary lobectomy and the subsequent histopathological examination of the surgical specimen revealed a poorly differentiated SCC. On postoperative week 4, the patient presented with purulent and bloody discharge from the left nostril and was misdiagnosed with an upper jaw cyst. After another 3 weeks, the patient was re-admitted to the hospital with a mass of left nostril and nasal congestion. Tru-Cut biopsies from the nasal area and histopathological examination revealed a moderately differentiated SCC. According to the clinical presentation and the histopathological findings, the patient was diagnosed with double primary cancer of the lung and the nasal vestibule. The mass of the left nostril was significantly reduced in size with radiotherapy. To the best of our knowledge, there is no similar case previously reported in the literature. Due to the rarity of scc of the nasal vestibule concomittant with lung cancer, we herein present this case report with a review of the relevant literature and investigation of the clinical characteristics.

Association of human leukocyte antigen DRB1 polymorphism and tuberculosis: a meta-analysis.

OBJECTIVE: To determine whether the human leukocyte antigen DRB1 (HLA-DRB1) is associated with clinical tuberculosis (TB). METHODS: Pooled odds ratios (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of the association between HLA-DRB1 alleles and risk of TB. The χ(2)-based Q-test and I(2) statistics were calculated to examine heterogeneity. Egger's test was performed for the assessment of publication bias. Subgroup analysis was performed based on ethnicity and genotyping methods. RESULTS: A total of 19 case-control studies with 16 alleles (HLA-DRB1*01-HLA-DRB1*16) were included in this meta-analysis. No significant publication bias was detected among these studies. The HLA-DRB1*03 (OR 0.77, 95%CI 0.64-0.93, P = 0.0057) showed a protective effect, while HLA-DRB1*04 (OR 1.24, 95%CI 1.00-1.55, P = 0.0494), HLA-DRB1*08 (OR 1.45, 95%CI 1.14-1.86, P = 0.0030) and HLA-DRB1*16 (OR 1.39, 95%CI 1.04-1.87, P = 0.0269) were significantly associated with increased TB occurrence. Subgroup analysis showed that both ethnicity and genotyping method affected the association between HLA-DRB1*03, HLA-DRB1*04 and HLA-DRB1*08 alleles and TB occurrence. CONCLUSION: These results reinforce the importance of HLA-DRB1 alleles in the development of infectious diseases.

Treatment of esophageal-gastric double primary cancer by pedunculated remnant gastric interposition, esophageal-gastric anastomosis and gastrojejunal Billroth II anastomosis: A case report.

With the continuous advancement of clinical diagnostic techniques, including imaging technology, the incidence of confirmed multiple primary cancers or double primary carcinoma increases yearly. However, studies reporting synchronization surgery performed for primary dual esophageal gastric cancer are rare. The present study reports the case of a patient with double primary esophageal-gastric cancer, located in the thoracic cavity segment of the esophagus and gastric antrum of the stomach, respectively. The gastric cancer was diagnosed by endoscopy biopsy with concomitant esophageal cancer. The patient underwent gastric cancer resection, and pedunculated remnant gastric interposition esophagogastric side anastomosis was performed with gastrojejunostomy Billroth II anastomosis behind the colon. Abdominal cavity lymph node dissection was also performed. The esophageal-gastric double primary cancer was simultaneously excised and the gastric regions were used in the construction of the upper gastrointestinal tract: The surgery was successful. However, two weeks after surgery, upper gastrointestinal imaging revealed esophagogastric anastomotic leakage. Subsequently, an esophageal stent was inserted and antibiotics and additional treatment was administered. Follow-up one year after surgery revealed that the patient was well and remained in a stable condition.

EFFICACY OF DIFFERENT RESECTIONS ON NON-MUSCLE-INVASIVE BLADDER CANCER AND ANALYSIS OF THE OPTIMAL SURGICAL METHOD.

This study aimed to analyze the clinical efficacy of different resections in treating non-muscle-invasive bladder cancer (NMIBC), including partial cystectomy, transurethral resection of bladder tumor (TURBT) and holmium laser resection of bladder tumor. Two hundred and sixteen patients were recruited with NMIBC who were available for follow-up visits in hospital, including 62 cases treated with partial cystectomy, 90 cases treated with TURBT and 64 cases with holmium laser resection. Analysis was made on the cases with tumor relapse in the two years, on operation time, blood loss, time for indwelling urinary catheter, hospital stay and complications after operation. Results were compared to the clinical efficacy of these operation patterns. It was found that the two-year relapse rate for TURBT group, partial cystectomy group and Holmium laser resection group was 41%, 31%, and 33% respectively, and the difference had no statistical significance (p>0.05). Both the TURBT group and holmium laser resection group had shorter operation time, hospital stay and time for indwelling urinary catheter as well as much less blood loss when compared with the partial cystectomy group; the difference had statistical significance (p<0.001). In terms of complications, the TURBT group was likely to induce obturator nerve reflex and bladder perforation while the partial cystectomy group was likely to induce bladder spasm. Therefore, this study presumes that holmium laser resection and TURBT are much safer and quicker for recovery and obviously superior to the partial cystectomy.

Development of high-speed and wide-angle visible observation diagnostics on Experimental Advanced Superconducting Tokamak using catadioptric optics.

A new wide-angle endoscope for visible light observation on the Experimental Advanced Superconducting Tokamak (EAST) has been recently developed. The head section of the optical system is based on a mirror reflection design that is similar to the International Thermonuclear Experimental Reactor-like wide-angle observation diagnostic on the Joint European Torus. However, the optical system design has been simplified and improved. As a result, the global transmittance of the system is as high as 79.6% in the wavelength range from 380 to 780 nm, and the spatial resolution is <5 mm for the full depth of field (4000 mm). The optical system also has a large relative aperture (1:2.4) and can be applied in high-speed camera diagnostics. As an important diagnostic tool, the optical system has been installed on the HT-7 (Hefei Tokamak-7) for its final experimental campaign, and the experiments confirmed that it can be applied to the investigation of transient processes in plasma, such as ELMy eruptions in H-mode, on EAST.

Oxidation pattern of small silicon oxide clusters: structures and stability of Si6On (n = 1-12).

We have performed systematic ab initio calculations to study the structures and stability of Si(6)O(n)() clusters (n = 1-12) in order to understand the oxidation process in silicon systems. Our calculation results show that oxidation pattern of the small silicon cluster, with continuous addition of O atoms, extends from one side to the entire Si cluster. Si atoms are found to be separated from the pure Si cluster one-by-one by insertion of oxygen into the Si-O bonds. From fragmentation energy analyses, it is found that the Si-rich clusters usually dissociate into a smaller pure Si clusters (Si(5), Si(4), Si(3), or Si(2)), plus oxide fragments such as SiO, Si(2)O(2), Si(3)O(3), Si(3)O(4), and Si(4)O(5). We have also studied the structures of the ionic Si(6)O(n)(+/-) (n = 1-12) clusters and found that most of ionic clusters have different lowest-energy structures in comparison with the neutral clusters. Our calculation results suggest that transformation Si(6)O(n)+(a) + O --> Si(6)O(n+1)+(a) should be easier.

Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains.

We used integrin alphaLbeta2 heterodimers containing I domains locked open (active) or closed (inactive) with disulfide bonds to investigate regulatory interactions among domains in integrins. mAbs to the alphaL I domain and beta2 I-like domain inhibit adhesion of wild-type alphaLbeta2 to intercellular adhesion molecule-1. However, with alphaLbeta2 containing a locked open I domain, mAbs to the I domain were subdivided into subsets (i) that did not inhibit, and thus appear to inhibit by favoring the closed conformation, and (ii) that did inhibit, and thus appear to bind to the ligand binding site. Furthermore, alphaLbeta2 containing a locked open I domain was completely resistant to inhibition by mAbs to the beta2 I-like domain, but became fully susceptible to inhibition after disulfide reduction with DTT. This finding suggests that the I-like domain indirectly contributes to ligand binding by regulating opening of the I domain in wild-type alphaLbeta2. Conversely, locking the I domain closed partially restrained conformational change of the I-like domain by Mn(2+), as measured with mAb m24, which we map here to the beta2 I-like domain. By contrast, locking the I domain closed or open did not affect constitutive or Mn(2+)-induced exposure of the KIM127 epitope in the beta2 stalk region. Furthermore, locked open I domains, in alphaLbeta2 complexes or expressed in isolation on the cell surface, bound to intercellular adhesion molecule-1 equivalently in Mg(2+) and Mn(2+). These results suggest that Mn(2+) activates alphaLbeta2 by binding to a site other than the I domain, most likely the I-like domain of beta2.

Amino acid residues in the PSI domain and cysteine-rich repeats of the integrin beta2 subunit that restrain activation of the integrin alpha(X)beta(2).

The leukocyte integrin alpha(X)beta(2) (p150,95) recognizes the iC3b complement fragment and functions as the complement receptor type 4. alpha(X)beta(2) is more resistant to activation than other beta(2) integrins and is inactive in transfected cells. However, when human alpha(X) is paired with chicken or mouse beta(2), alpha(X)beta(2) is activated for binding to iC3b. Activating substitutions were mapped to individual residues or groups of residues in the N-terminal plexin/semaphorin/integrin (PSI) domain and C-terminal cysteine-rich repeats 2 and 3. These regions are linked by a long range disulfide bond. Substitutions in the PSI domain synergized with substitutions in the cysteine-rich repeats. Substitutions T4P, T22A, Q525S, and V526L gave full activation. Activation of binding to iC3b correlated with exposure of the CBR LFA-1/2 epitope in cysteine-rich repeat 3. The data suggest that the activating substitutions are present in an interface that restrains the human alpha(X)/human beta(2) integrin in the inactive state. The opening of this interface is linked to structural rearrangements in other domains that activate ligand binding.

Structural and functional studies with antibodies to the integrin beta 2 subunit. A model for the I-like domain.

To establish a structure and function map of the beta2 integrin subunit, we mapped the epitopes of a panel of beta2 monoclonal antibodies including function-blocking, nonblocking, and activating antibodies using human/mouse beta2 subunit chimeras. Activating antibodies recognize the C-terminal half of the cysteine-rich region, residues 522-612. Antibodies that do not affect ligand binding map to residues 1-98 and residues 344-521. Monoclonal antibodies to epitopes within a predicted I-like domain (residues 104-341) strongly inhibit LFA-1-dependent adhesion. These function-blocking monoclonal antibodies were mapped to specific residues with human --> mouse knock-out or mouse --> human knock-in mutations. Combinatorial epitopes involving residues distant in the sequence provide support for a specific alignment between the beta-subunit and I domains that was used to construct a three-dimensional model. Antigenic residues 133, 332, and 339 are on the first and last predicted alpha-helices of the I-like domain, which are adjacent on its "front." Other antigenic residues in beta2 and in other integrin beta subunits are present on the front. No antigenic residues are present on the "back" of the domain, which is predicted to be in an interface with other domains, such as the alpha subunit beta-propeller domain. Most mutations in the beta2 subunit in leukocyte adhesion deficiency are predicted to be buried in the beta2 subunit I-like domain. Two long insertions are present relative to alpha-subunit I-domains. One is tied down to the back of the I-like domain by a disulfide bond. The other corresponds to the "specificity-determining loop" defined in beta1 and beta3 integrins and contains the antigenic residue Glu(175) in a disulfide-bonded loop located near the "top" of the domain.