Diagnostic accuracy of a prehospital electrocardiogram rule-based algorithm for ST-elevation myocardial infarction: results from a population-wide project.

INTRODUCTION: This study reviewed the diagnostic accuracy of the prehospital electrocardiogram (PHECG) rule-based algorithm for ST-elevation myocardial infarction (STEMI) universally utilised in Hong Kong. METHODS: This prospective observational study was linked to a population-wide project. We analysed 2210 PHECGs performed on patients who presented to the emergency medical service (EMS) with chest pain from 1 October to 31 December 2021. The diagnostic accuracy of the adopted rulebased algorithm, the Hannover Electrocardiogram System, was evaluated using the adjudicated blinded rating by two investigators as the primary reference standard. Diagnostic accuracy was also evaluated using the attending emergency physician's diagnosis and the diagnosis on hospital discharge as secondary reference standards. RESULTS: The prevalence of STEMI was 5.1% (95% confidence interval [CI]=4.2%-6.1%). Using the adjudicated blinded rating by investigators as the reference standard, the rule-based PHECG algorithm had a sensitivity of 94.6% (95% CI=88.2%-97.8%), specificity of 87.9% (95% CI=86.4%-89.2%), positive predictive value of 29.4% (95% CI=24.8%-34.4%), and negative predictive value of 99.7% (95% CI=99.3%-99.9%) [all P<0.05]. CONCLUSION: The rule-based PHECG algorithm that is widely used in Hong Kong demonstrated high sensitivity and fair specificity for the diagnosis of STEMI.

[Genomic structure of varicella-zoster virus and its vaccine application status].

With the determination of the whole genome sequence of varicella-zoster virus (VZV) virus, the successful breakthrough of infectious cloning technology of VZV, and the emergence of effective preventive vaccines, which have been proven to be effective and safe, varicella has become a disease preventable by specific immunity. This article will review the genomic structure, epidemiological characteristics, and research application progress of varicella vaccine and herpes zoster vaccine of varicella zoster virus to provide reference for primary prevention of the disease.

[Progress on health-related quality of life and its influencing factors in patients with tuberculosis sequelae].

With the emergence of new tuberculosis patients, the number of patients with tuberculosis sequelae is increasing, which not only increases the medical burden of tuberculosis sequelae year by year, but also affects the health-related quality of life (HRQOL) of patients. The HRQOL of patients with tuberculosis sequelae has gradually received attention, but there are few relevant studies. Studies have shown that HRQOL is related to various factors such as post-tuberculosis lung disease, adverse reaction to anti-tuberculosis drugs, decreased physical activity, psychological barriers, low economic status and marital status. This article reviewed the current situation of HRQOL in patients with sequelae of tuberculosis and its influencing factors, in order to provide a reference for improving the quality of life of patients with sequelae of tuberculosis.

XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer.

The common participation of oncogenic KRAS proteins in many of the most lethal human cancers, together with the ease of detecting somatic KRAS mutant alleles in patient samples, has spurred persistent and intensive efforts to develop drugs that inhibit KRAS activity. However, advances have been hindered by the pervasive inter- and intra-lineage diversity in the targetable mechanisms that underlie KRAS-driven cancers, limited pharmacological accessibility of many candidate synthetic-lethal interactions and the swift emergence of unanticipated resistance mechanisms to otherwise effective targeted therapies. Here we demonstrate the acute and specific cell-autonomous addiction of KRAS-mutant non-small-cell lung cancer cells to receptor-dependent nuclear export. A multi-genomic, data-driven approach, utilizing 106 human non-small-cell lung cancer cell lines, was used to interrogate 4,725 biological processes with 39,760 short interfering RNA pools for those selectively required for the survival of KRAS-mutant cells that harbour a broad spectrum of phenotypic variation. Nuclear transport machinery was the sole process-level discriminator of statistical significance. Chemical perturbation of the nuclear export receptor XPO1 (also known as CRM1), with a clinically available drug, revealed a robust synthetic-lethal interaction with native or engineered oncogenic KRAS both in vitro and in vivo. The primary mechanism underpinning XPO1 inhibitor sensitivity was intolerance to the accumulation of nuclear IκBα (also known as NFKBIA), with consequent inhibition of NFκB transcription factor activity. Intrinsic resistance associated with concurrent FSTL5 mutations was detected and determined to be a consequence of YAP1 activation via a previously unappreciated FSTL5-Hippo pathway regulatory axis. This occurs in approximately 17% of KRAS-mutant lung cancers, and can be overcome with the co-administration of a YAP1-TEAD inhibitor. These findings indicate that clinically available XPO1 inhibitors are a promising therapeutic strategy for a considerable cohort of patients with lung cancer when coupled to genomics-guided patient selection and observation.

Applications and future directions for optical coherence tomography in dermatology.

Optical coherence tomography (OCT) is a noninvasive optical imaging method that can generate high-resolution en face and cross-sectional images of the skin in vivo to a maximum depth of 2 mm. While OCT holds considerable potential for noninvasive diagnosis and disease monitoring, it is poorly understood by many dermatologists. Here we aim to equip the practising dermatologist with an understanding of the principles of skin OCT and the potential clinical indications. We begin with an introduction to the technology and discuss the different modalities of OCT including angiographic (dynamic) OCT, which can image cutaneous blood vessels at high resolution. Next we review clinical applications. OCT has been most extensively investigated in the diagnosis of keratinocyte carcinomas, particularly basal cell carcinoma. To date, OCT has not proven sufficiently accurate for the robust diagnosis of malignant melanoma; however, the evaluation of abnormal vasculature with angiographic OCT is an area of active investigation. OCT, and in particular angiographic OCT, also shows promise in monitoring the response to therapy of inflammatory dermatoses, such as psoriasis and connective tissues disease. We additionally discuss a potential role for artificial intelligence in improving the accuracy of interpretation of OCT imaging data.

[Effect and mechanism of siRNA targeting α-enolase gene combined with paclitaxel on proliferation, invasion and apoptosis of hepatocellular carcinoma cell].

Objective: To investigate the effect of siRNA targeting inhibition of α-enolase (ENO1) combined with paclitaxel on the proliferation, invasion and apoptosis of hepatocellular carcinoma SK-HEP-1 cell and its mechanism. Methods: siRNA-ENO1 (siRNA-ENO1 group) and siRNA-negative control (siRNA-NC group) were transfected into SK-HEP-1 cells in vitro, the untransfected SK-HEP-1 cells were used as the control group, and the transfection effect was detected by real-time fluorescent quantitative polymerase chain reaction and western blotting. After SK-HEP-1 cells were treated with 0, 2.5, 5, 10, 20 and 40 µg/L paclitaxel for 48 hours, the cell survival rate was measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) method and the semi inhibitory concentration of paclitaxel was calculated. SK-HEP-1 cells transfected with siRNA-ENO1 or siRNA-NC were treated with 10 µg/L paclitaxel as paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group. The proliferation, clonogenesis, invasion and apoptosis of siRNA-NC group, siRNA-ENO1 group, paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group were detected by MTT, clonogenesis, Transwell chamber and flow cytometry respectively. The expression levels of the phosphorylation of phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (Akt) and proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9) and B lymphocytoma-2 gene (Bcl-2) were detected by western blotting. Results: Compared with the control group (1.00±0.00 and 0.69±0.04, respectively), the expression levels of ENO1 mRNA and protein (0.25±0.03 and 0.23±0.02, respectively) in siRNA-ENO1 group decreased significantly (P<0.05), but there were no significant differences in the expression levels of ENO1 mRNA and protein in siRNA-NC group (P>0.05). Compared without treatment group [(100.00±0.00)%, P<0.05], the survival rates of SK-HEP-1 cells treated with 2.5, 5, 10, 20 and 40 µg/L paclitaxel [(88.65±6.46)%, (72.36±6.08)%, (60.48±4.23)%, (38.52±3.56)% and (20.75±2.32)%, respectively] decreased significantly (P<0.05), and the semi inhibitory concentration of paclitaxel was 13.26 µg/L. The cell survival rate and clone formation rate of siRNA-ENO1 group [(68.86±5.12)% and (18.12±2.25)%, respectively] were lower than those of siRNA-NC group [(100.00±0.00)% and (29.65±3.06)%, respectively, P<0.05]. The cell survival rate and clone formation rate of the paclitaxel+ siRNA-ENO1 group [(43.28±2.64)% and (8.72±0.52)%, respectively] were significantly different from those of the paclitaxel+ siRNA-NC group [(61.75±5.06)% and (13.48±2.16)%, respectively, P<0.05] and siRNA-ENO1 groups [(68.86±5.12)% and (18.12±2.25)%, respectively, P<0.05]. Cell invasion number in paclitaxel+ siRNA-ENO1 group (23.64±2.12) was lower than that in siRNA-ENO1 group and paclitaxel+ siRNA-NC group (42.16±2.75 and 37.35±2.42, respectively, P<0.05). The apoptosis rates of paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively] were higher than that of siRNA-NC group [(7.21±0.70)%, P<0.05]. The apoptosis rate in the paclitaxel+ siRNA-ENO1 group [(24.59±2.40)%] was higher than those in the paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively, P<0.05]. The expression levels of ENO1, PI3K/Akt signaling pathway related proteins including p-PI3K and p-Akt and the expression levels of PCNA, MMP-9 and Bcl-2 in siRNA-ENO1 group and paclitaxel+ siRNA-NC group were lower than those in siRNA-NC group (P<0.05). The expression levels of ENO1, p-PI3K, p-Akt, PCNA, MMP-9 and Bcl-2 in paclitaxel+ siRNA-ENO1 group were lower than those in siRNA-ENO1 group or paclitaxel+ siRNA-NC group (P<0.05). Conclusion: siRNA targeting inhibition of ENO1 expression can enhance the inhibitory effect of paclitaxel on proliferation, invasion and apoptosis of SK-HEP-1 cells, and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

[Association between ocular dominance and refraction in myopic subjects].

Objective: To determine the association between ocular dominance and myopic-astigmatic characteristics in myopic subjects. Methods: Cross-sectional study. A total of 1 503 myopic subjects visiting from the myopiac clinic from December 2011 to December 2012 were included. The spheres and cylinders were recorded. The ocular dominance was determined by the hole-in-the-card test. The average spherical equivalent (SE) and the cylinder between the dominant eyes and the non-dominant eyes were compared with the paired t test. The associations between ocular dominance laterality and refractive characters were analyzed with the crosstab Chi-square test. Results: There were 527 males and 976 females in this study. The median (min, max) of age was 24 (17, 49) years old. Among the subjects, 66.00% (992/1 503) of subjects were right-eye dominant, while 34.00% (511/1 503) of subjects were left-eye dominant. The dominant eyes had significantly lower average sphere powers ï¼»(-5.01±1.91) D vs. (-5.10±1.99) Dï¼½ and lower average cylinder powers ï¼»(-0.70±0.68) D vs. (-0.76±0.73) Dï¼½ than the non-dominant eyes (t=2.976, 4.319; both P<0.01). In the subgroups of |ΔSE|≤0.50 D, 0.50 D<|ΔSE|≤1.00 D, 1.00 D<|ΔSE|≤2.00 D and |ΔSE|>2.00 D, respectively, the dominant eyes were lower myopic in 49.37% (355/719), 51.10% (163/319), 58.48% (100/171) and 65.56% (59/90) of the subjects. The inter-group difference was statistically significant (χ²=11.588, P=0.009). In the subgroups of |ΔCyl|≤0.25 D, 0.25 D<|ΔCyl|≤0.50 D and |ΔCyl|>0.50 D, the dominant eyes had lower astigmatism in 53.94% (89/165), 65.66% (65/99) and 69.70% (46/66) of the subjects, respectively. The inter-group difference was statistically significant (χ²=6.414, P=0.040). Conclusion: The ocular dominance laterality is significantly associated with lower myopia and lower astigmatism in the myopic subjects. (Chin J Ophthalmol, 2020, 56: 693-698).

Hybrid oncocytic/chromophobe renal tumors are molecularly distinct from oncocytoma and chromophobe renal cell carcinoma.

Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney represents a poorly understood clinicopathologic entity with pathologic features that overlap between benign renal oncocytoma (RO) and malignant chromophobe renal cell carcinoma (ChRCC). Consequently, characterization of HOCT and its separation from the foregoing entities are clinically important. The aim of this study was to describe the pathologic and molecular features of HOCT and to compare them with those of RO and ChRCC. We retrospectively identified a cohort of 73 cases with renal oncocytic tumors (19 RO, 27 HOCT, and 27 ChRCC) for whom clinical follow-up data were available by 2 tertiary care hospitals. All cases were sporadic except for 2 HOCTs that were associated with Birt-Hogg-Dubé syndrome. Lesional tissues were retrieved for molecular analysis. We performed targeted gene sequencing of all exons of 261 cancer related genes on a subset of HOCT samples (n = 16). Gene expression profiling of a customized codeset was conducted on 19 RO, 24 HOCT, and 27 ChRCC samples. Clinicopathologic characteristics as well as DNA copy number alterations, mutational and transcriptional features of HOCT derived from sequencing and expression profiling data are described and compared to those in RO and ChRCC. HOCTs were more frequently multifocal and did not exhibit mutations in genes that are recurrently mutated in RO or ChRCC but showed copy number alterations primarily involving losses in chromosomes 1 and X/Y. The mRNA transcript data show that HOCT can be separated from RO and ChRCC. Hence, HOCT appears to represent a distinct renal tumor entity with genomic features that are intermediate between those of RO and ChRCC.

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.

MicroRNA-101 regulates autophagy, proliferation and apoptosis via targeting EZH2 in laryngeal squamous cell carcinoma.

Laryngeal carcinoma is the second commonest head and neck carcinoma globally. MicroRNA-101 (miR-101) has been reported as a tumor suppressor in multiple malignancies including laryngeal squamous cell carcinoma (LSCC). However, the roles and molecular mechanisms of miR-101 in the development of LSCC have not been fully elucidated. In present study, RT-qPCR assay was performed to detect the expression of miR-101 and enhancer of zeste homolog 2 (EZH2) mRNA. Western blot assay was conducted to determine protein expression of LC3-Ⅰ, LC3-Ⅱ, p62 and EZH2. Cell proliferative capacity was evaluated by MTS assay. The effect of miR-101 alone or along with EZH2 on cell apoptosis was assessed by apoptotic index and caspase-3 activity. Bioinformatic analysis, luciferase assay and RNA immunoprecipitation (RIP) assay were carried out to investigate the interaction between miR-101 and EZH2. Results revealed that miR-101 expression was strikingly down-regulated in LSCC cell lines. Functional analyses showed that ectopic expression of miR-101 suppressed cell autophagy and proliferation and facilitated cell apoptosis in LSCC. Further investigations revealed that miR-101 inhibited EZH2 expression by direct interaction and EZH2 was highly expressed in LSCC cells. Also, EZH2 knockdown reduced the autophagic activity of LSCC cells. Moreover, restoration experiments showed that EZH2 up-regulation weakened miR-101-mediated anti-autophagy, anti-proliferation and pro-apoptosis effects in LSCC cells. In conclusion, our findings suggested that miR-101 inhibited autophagy and proliferation and promoted apoptosis via targeting EZH2 in LSCC, providing a deep insight into the pathogenesis of LSCC and hinting the pivotal roles of epigenetic modifications especially histone methylation in the development of LSCC.

[Value of ceramide in the diagnosis and risk prediction of coronary artery disease].

Objective: To evaluate the clinical values of 4 types of ceramides (Cer1, Cer2, Cer3, Cer4) in the coronary artery stenosis, clinical diagnosis and risk prediction. Methods: A total of 890 patients with coronary heart disease (CHD) in Beijing Anzhen Hospital between March 2018 and August 2018 were enrolled. The relationships between different degrees of coronary artery stenosis and ceramide levels was investigated. Diagnostic value of ceramides on acute myocardial infarction was analyzed. Meanwhile, Major adverse cardiac and cerebrovascular events (MACCE) in 1 year after discharging were collected to evaluate the predictive value of ceramides on risk of CHD and stroke. Results: This study showed that there were no significant differences of ceramide levels in CHD patients with different degrees of coronary artery stenosis (P>0.05), and the area under receiver operating characteristic (ROC) curve in the diagnosis of acute myocardial infarction patients was 0.725. Conclusions: Ceramide is proved to be helpful in the diagnosis of acute myocardial infarction and MACCE prediction. The relationships between ceramide and degrees of coronary artery stenosis as well as the prognosis of CHD need further elucidation.

Low-to-High Confinement Transition Mediated by Turbulence Radial Wave Number Spectral Shift in a Fusion Plasma.

A new model for the low-to-high (L-H) confinement transition has been developed based on a new paradigm for turbulence suppression by velocity shear [G. M. Staebler et al., Phys. Rev. Lett. 110, 055003 (2013)]. The model indicates that the L-H transition can be mediated by a shift in the radial wave number spectrum of turbulence, as evidenced here, for the first time, by the direct observation of a turbulence radial wave number spectral shift and turbulence structure tilting prior to the L-H transition at tokamak edge by direct probing. This new mechanism does not require a pretransition overshoot in the turbulent Reynolds stress, shunting turbulence energy to zonal flows for turbulence suppression as demonstrated in the experiment.

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.

Neutral alpha-1,4-glucosidase and fructose levels contribute to discriminating obstructive and nonobstructive azoospermia in Chinese men with azoospermia.

Nowadays, whether neutral alpha-1,4-glucosidase (NAG) and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese azoospermic patients remains unclear. In this study, we retrospectively analysed the levels of NAG and fructose in 229 patients with obstructive azoospermia and 415 patients with nonobstructive azoospermia from three different medical central. Results indicated that NAG and fructose levels in patients with nonobstructive azoospermia were significantly higher compared with those with obstructive azoospermia (P < 0.05). According to the reference value of NAG and fructose defined by the World Health Organization (WHO, 2010), decreased level of NAG was observed in 77.3% of patients with obstructive azoospermia, which was significantly higher than those with nonobstructive azoospermia (55.2%, P < 0.0001). Low level of fructose was observed in 48.0% of patients with obstructive azoospermia, which is also obviously higher than those with nonobstructive azoospermia (31.8%, P < 0.0001). Moreover, the decrease of both NAG and fructose was only recorded in 3.7% of patients with SCO syndrome, 5.0% of patients with severe hypospermatogenesis and 18.2% of patients with maturation arrest. Therefore, our results indicated that NAG and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese patients based on the histological types of testes.

[Value of prostate volume, PSAD and F/T in the detection of prostate cancer in males with PSA 4-10 µg/L].

OBJECTIVE: To evaluate the association of prostate volume, PSAD and F/T with prostate cancer detection rate in males with a total PSA of 4-10 µg/L. METHODS: Clinical data of 196 patients who underwent prostate biopsy from November 2006 to September 2010 and with a PSA of 4-10 µg/L were retrospectively analyzed. The association of detection rate of prostate cancer with prostate volume, prostate specific antigen density PSAD) and free PSA/total PSA ratio (F/T) was analyzed by Spearman coefficient, receiver operating characteristic curve and logistic regression analysis. RESULTS: The prostate volume, PSAD and F/T had a significant association with detection rate of prostate cancer (P<0.05 for all). The odd ratio was 0.96, 1.91 and 0.02, respectively. The area under curve (AUR) was 0.31, 0.66 and 0.63, respectively. The cancer detection rate was decreased along with the increase of prostate volume. When PSAD 0.15 ng·ml(-1)·ml(-1) was used as the cut-off value, the sensitivity, specificity, positive prediction rate and negative prediction rate was 72.3%, 51.1%, 42.3% and 21.2%, respectively. When the patients were divided by prostate volume into <19.9, 20-39.9, 40-59.9, 60-79.9 and >80 ml subgroups, the cancer detection rate of each subgroup was 50.0%, 45.6%, 30.8%, 15.4% and 5.6%, respectively. CONCLUSION: In patients with a total PSA of 4-10 µg/L, the prostate cancer detection rate has a significant association with prostate volume, PSAD and F/T.

New steady-state quiescent high-confinement plasma in an experimental advanced superconducting tokamak.

A critical challenge facing the basic long-pulse high-confinement operation scenario (H mode) for ITER is to control a magnetohydrodynamic (MHD) instability, known as the edge localized mode (ELM), which leads to cyclical high peak heat and particle fluxes at the plasma facing components. A breakthrough is made in the Experimental Advanced Superconducting Tokamak in achieving a new steady-state H mode without the presence of ELMs for a duration exceeding hundreds of energy confinement times, by using a novel technique of continuous real-time injection of a lithium (Li) aerosol into the edge plasma. The steady-state ELM-free H mode is accompanied by a strong edge coherent MHD mode (ECM) at a frequency of 35-40 kHz with a poloidal wavelength of 10.2 cm in the ion diamagnetic drift direction, providing continuous heat and particle exhaust, thus preventing the transient heat deposition on plasma facing components and impurity accumulation in the confined plasma. It is truly remarkable that Li injection appears to promote the growth of the ECM, owing to the increase in Li concentration and hence collisionality at the edge, as predicted by GYRO simulations. This new steady-state ELM-free H-mode regime, enabled by real-time Li injection, may open a new avenue for next-step fusion development.

729G/C polymorphism in Toll-like receptor 4 results in increased susceptibility to bladder cancer.

In this study, the association between the 729G/C polymorphism in Toll-like receptor 4 (TLR4) and the risk of bladder cancer was investigated. A total of 376 patients with bladder cancer and 380 healthy volunteers from the Third Xiangya Hospital of Central South University (China) were enrolled in this study between January 2008 and February 2014. The TLR4-729G/C polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism assay. There was a significant difference in the distribution of the TLR4-729G/C genotype between bladder cancer patients and healthy controls (P < 0.001). Our analysis showed that the GC genotype (OR = 2.99; 95%CI = 1.01-4.81, P = 0.046) and CC genotype (OR = 3.67; 95%CI = 2.11-7.27, P = 0.017) were significantly associated with increased bladder cancer risk when the GG genotype served as a reference. Furthermore, carriers of the C allele had a significantly increased risk of developing bladder cancer (OR = 3.89; 95%CI = 2.88-8.53; P = 0.009). Our results suggest a correlation between the TLR4-729G/C polymorphism and the risk of developing bladder cancer in this Chinese population.

Increasing the tolerance of DCD hearts to warm ischemia by pharmacological postconditioning.

Donation after circulatory death (DCD) offers a potential additional source of cardiac allografts. We used a porcine asphyxia model to evaluate viability of DCD hearts subjected to warm ischemic times (WIT) of 20­40 min prior to flushing with Celsior (C) solution. We then assessed potential benefits of supplementing C with erythropoietin, glyceryl trinitrate and zoniporide (Cs), a combination that we have shown previously to activate ischemic postconditioning pathways. Hearts flushed with C/Cs were assessed for functional, biochemical and metabolic recovery on an ex vivo working heart apparatus. Hearts exposed to 20-min WIT showed full recovery of functional and metabolic profiles compared with control hearts (no WIT). Hearts subjected to 30- or 40-min WIT prior to C solution showed partial and no recovery, respectively. Hearts exposed to 30-min WIT and Cs solution displayed complete recovery, while hearts exposed to 40-min WIT and Cs solution demonstrated partial recovery. We conclude that DCD hearts flushed with C solution demonstrate complete recovery up to 20-min WIT after which there is rapid loss of viability. Cs extends the limit of WIT tolerability to 30 min. DCD hearts with ≤30-min WIT may be suitable for transplantation and warrant assessment in a transplant model.

Role of cathepsin B in regulating migration and invasion of fibroblast-like synoviocytes into inflamed tissue from patients with rheumatoid arthritis.

Cathepsin B (CB), an important proteinase that participates in joint destruction in rheumatoid arthritis (RA), exhibits higher expression in fibroblast-like synoviocyte (FLS) of abnormal proliferative synovial tissues. Whether and how it affects the biological behaviours of RA-FLS, such as migration and invasion, are poorly understood. In the present study, CB expression in synovial tissues of patients with RA and ostearthritis (OA) were measured by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. Stable depletion of endogenous CB was achieved by small interfering RNA (siRNA) transfection, and decrease of CB activity was acquired by using its specific inhibitor (CA074Me). The effects of CA074Me and RNA interference (RNAi) treatments on proliferation, migration, invasion, matrix metalloproteinase (MMP)-2/-9 expression, focal adhesion kinase (FAK) activation, and mitogen-activated protein kinases (MAPKs) phosphorylation of FLS were analysed. In RA synovial tissues, CB was expressed at elevated levels compared with OA synovial tissues. CA074Me could inhibit invasion of FLS obtained from RA patients in an ex-vivo invasion model. CA074Me and siRNA treatments suppressed the migration and invasion of FLS, reduced the activity, expression and mRNA level of MMP-2, restrained the activation of FAK and reduced the expression of F-actin. Moreover, CA074Me decreased the phosphorylation of P38 MAPK and c-Jun N-terminal kinase (JNK) in FLS, while siCB treatment reduced the phosphorylation of P38 but not JNK. CB substantially contributes to the invasive phenotype of FLS that leads to joint destruction in RA. This proteinase may show promise as a therapeutic target in inflammatory arthritis.

New edge coherent mode providing continuous transport in long-pulse H-mode plasmas.

An electrostatic coherent mode near the electron diamagnetic frequency (20-90 kHz) is observed in the steep-gradient pedestal region of long pulse H-mode plasmas in the Experimental Advanced Superconducting Tokamak, using a newly developed dual gas-puff-imaging system and diamond-coated reciprocating probes. The mode propagates in the electron diamagnetic direction in the plasma frame with poloidal wavelength of ∼8 cm. The mode drives a significant outflow of particles and heat as measured directly with the probes, thus greatly facilitating long pulse H-mode sustainment. This mode shows the nature of dissipative trapped electron mode, as evidenced by gyrokinetic turbulence simulations.