Spinful Topological Phases in Acoustic Crystals with Projective PT Symmetry.

For the classification of topological phases of matter, an important consideration is whether a system is spinless or spinful, as these two classes have distinct symmetry algebra that gives rise to fundamentally different topological phases. However, only recently has it been realized theoretically that in the presence of gauge symmetry, the algebraic structure of symmetries can be projectively represented, which possibly enables the switch between spinless and spinful topological phases. Here, we report the experimental demonstration of this idea by realizing spinful topological phases in "spinless" acoustic crystals with projective space-time inversion symmetry. In particular, we realize a one-dimensional topologically gapped phase characterized by a 2Z winding number, which features double-degenerate bands in the entire Brillouin zone and two pairs of degenerate topological boundary modes. Our Letter thus overcomes a fundamental constraint on topological phases by spin classes.

Observation of Dirac Hierarchy in Three-Dimensional Acoustic Topological Insulators.

Dirac cones (DCs) play a pivotal role in various unique phenomena ranging from massless electrons in graphene to robust surface states in topological insulators (TIs). Recent studies have theoretically revealed a full Dirac hierarchy comprising an eightfold bulk DC, a fourfold surface DC, and a twofold hinge DC, associated with a hierarchy of topological phases including first-order to third-order three-dimensional (3D) topological insulators, using the same 3D base lattice. Here, we report the first experimental observation of the Dirac hierarchy in 3D acoustic TIs. Using acoustic measurements, we unambiguously reveal that lifting of multifold DCs in each hierarchy can induce two-dimensional topological surface states with a fourfold DC in a first-order 3D TI, one-dimensional topological hinge states with a twofold DC in a second-order 3D TI, and zero-dimensional topological corner states in a third-order 3D TI. Our Letter not only expands the fundamental research scope of Dirac physics, but also opens up a new route for multidimensional robust wave manipulation.

Arachidonic acid products in airway nociceptor activation during acute lung injury.

We have reported that airway nociceptors [C fibre receptors (CFRs) and high-threshold Aδ fibre receptors (HTARs)] are activated during oleic acid (OA)-induced acute lung injury. In the present studies, we tested the hypothesis that this nociceptor activation is mediated by arachidonic acid products. In anaesthetized, open-chest, mechanically ventilated rabbits, we examined the response of the nociceptors to intravenous injection of OA before and after blocking the cyclo-oxygenase pathways with indomethacin. Pretreatment with indomethacin (20 mg kg(-1)) decreased the background activities of both CFRs (from 0.48 ± 0.12 to 0.25 ± 0.08 impulses/s, n = 7, P < 0.05) and HTARs (from 0.54 ± 0.14 to 0.23 ± 0.08 impulses/s, n = 10, P < 0.01). It also blocked the response of the nociceptors to OA. Likewise, pretreatment with thromboxane synthase inhibitor (ketoconazole) also blocked the nociceptor response to OA. In addition, local microinjection or intravenous injection of a thromboxane mimetic stimulated CFRs and HTARs. The present results clearly indicate that arachidonic acid metabolites mediate airway nociceptor activation during OA-induced acute lung injury and suggest that thromboxane may be a key mediator.

Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells.

Recently, salidroside (p-hydroxyphenethyl-beta-d-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

A preliminary study: the anti-proliferation effect of salidroside on different human cancer cell lines.

Salidroside (p-hydroxyphenethyl-beta-d-glucoside), which is present in all species of the genus Rhodiola, has been reported to have a broad spectrum of pharmacological properties. The present study, for the first time, focused on evaluating the effects of the purified salidroside on the proliferation of various human cancer cell lines derived from different tissues, and further investigating its possible molecular mechanisms. Cell viability assay and [(3)H] thymidine incorporation were used to evaluate the cytotoxic effects of salidroside on cancer cell lines, and flow cytometry analyzed the change of cell cycle distribution induced by salidroside. Western immunoblotting further studied the expression changes of cyclins (cyclin D1 and cyclin B1), cyclin-dependent kinases (CDK4 and Cdc2), and cyclin-dependent kinase inhibitors (p21(Cip1) and p27(Kip1)). The results showed that salidroside inhibited the growth of various human cancer cell lines in concentration- and time-dependent manners, and the sensitivity to salidroside was different in those cancer cell lines. Salidroside could cause G1-phase or G2-phase arrest in different cancer cell lines, meanwhile, salidroside resulted in a decrease of CDK4, cyclin D1, cyclin B1 and Cdc2, and upregulated the levels of p27(Kip1) and p21(Cip1). Taken together, salidroside could inhibit the growth of cancer cells by modulating CDK4-cyclin D1 pathway for G1-phase arrest and/or modulating the Cdc2-cyclin B1 pathway for G2-phase arrest.

Effects of arachidonic acid metabolites on airway sensors.

Arachidonic acid (AA) in the cell membrane produces a variety of metabolites by different enzymatic pathways. These lipid metabolites, along with other mediators, play an important role in the inflammatory processes. Many of them can bind directly to the receptors on the sensory endings and initiate electrical impulses to be transmitted to the central nervous system, causing reflex responses. These bioactive AA metabolites may also alter the lung mechanics (mechanical environment of the sensory ending), and in turn, stimulate sensory afferents. In addition, some metabolites may sensitize the sensory endings and make them more responsive to other mechanical or chemical stimulation. These metabolites may also induce other mediators and modulators to cause physiological effects. Furthermore, some of them may attract inflammatory cells to produce a localized effect. In short, AA metabolites may come from different sources and act through multiple pathways to stimulate airway sensors. This brief review is intended to illustrate the underlying mechanisms and help elucidate the inflammatory process in the airways.

Behaviours of pulmonary sensory receptors during development of acute lung injury in the rabbit.

We tested the hypothesis that oleic acid-induced acute lung injury activates pulmonary nociceptors, that is, C fibre receptors (CFRs) and high-threshold Adelta fibre receptors (HTARs). Single-unit activity was recorded in the cervical vagus nerve and assessed before and after injecting oleic acid (75 microl kg(-1) i.v.) into anaesthetized, open-chest, mechanically ventilated rabbits. Unit activities increased within seconds and peaked within a few minutes (from 0.3 +/- 0.1 to 1.4 +/- 0.9 impulses s(-1) for CFRs and from 0.5 +/- 0.1 to 1.7 +/- 0.3 impulses s(-1) for HTARs, both n = 8 and P < 0.05). These activities were sustained while pulmonary oedema developed and dynamic lung compliance decreased over the 90 min observation period. Activities in slowly adapting receptors and rapidly adapting receptors were also increased; however, their responsiveness to airway pressure stimulation decreased progressively. We conclude that pulmonary nociceptors are stimulated during acute lung injury. The dual nociceptor system, consisting of both non-myelinated CFRs and myelinated HTARs, may play an important role in the pathophysiological process of acute lung injury-induced respiratory responses.

Airway nociceptors activated by pro-inflammatory cytokines.

The present studies evaluate whether the vagus nerves link the lungs' immune and neural systems by transmitting information through pulmonary nociceptors. Single unit activities from pulmonary nociceptors [C fiber receptors (CFRs) and high threshold Adelta fiber receptors (HTARs)] were recorded from the cervical vagus nerve in anesthetized, open-chest, and mechanically ventilated rabbits. Interleukin1beta was then injected into the nociceptor field (IL-1beta, 10 microg/ml, 20 microl). Both CFRs and HTARs were stimulated by the local injection; their activities increased from 0.2+/-0.1 to 1.8+/-0.5 imp/s (n=10; p<0.01), and from 0.2+/-0.1 to 1.1+/-0.1 imp/s, respectively (n=6; p<0.01). These increases were greatly attenuated by simultaneous administration of IL-1beta with IL-1 ra, a natural IL-1 receptor antagonist. The nociceptors were not stimulated by local injection of normal saline. Our data demonstrate that nociceptors can be activated by pro-inflammatory cytokines and support the hypothesis that airway nociceptors transmit immune signals from the lung to the brain.

Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues.

N-myc downstream-regulated gene 2 (NDRG2) is believed to be involved in cell growth events. However, its exact function is still unknown. To elucidate the role of this gene, we used an anti-Ndrg2 monoclonal antibody in immunohistochemistry and immunofluorescence assays to analyze the expression pattern of Ndrg2 protein in mouse embryos at various gestational ages and in a variety of adult mouse tissues. Ndrg2 immunoreactivity was generally localized to the cytoplasm. During mouse development, Ndrg2 expression was observed in many developing tissues and organs including the heart, brain, lung, gut, liver, kidney, skeletal muscle, cartilage, chorion, epidermis, and whisker follicles. Ndrg2 expression was developmentally dynamic, being generally lower in the early stages of development and markedly increasing during later stages. Ndrg2 expression was also observed in a variety of adult mouse tissues, particularly in the heart and brain. This is the first demonstration of Ndrg2 protein expression in both embryonic and adult mouse tissues. Our results suggest that NDRG2 plays important roles in histogenesis and organogenesis.

[Multiple organ dysfunction scoring system: comparison and evaluation of correlation and accuracy of the three scoring systems in predicting the outcome of multiple organ dysfunction syndrome on highland].

OBJECTIVE: To study the characteristics of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome on plateau (H-ARDS/MODS) and compare the accuracy of the three MODS scoring criteria in predicting the outcome of syndrome. METHODS: Five hundred and forty cases fulfilling the criteria of MODS were divided into four groups according to the altitude of their inhabitation area: control group (on plain, CG, n=113, altitude: <430 m), moderate high altitude group 1 (H1G, n=314, altitude: 1,517 m), moderate high altitude group 2 (H2G, n=78, altitude: 2,261 m to 2,400 m) and high altitude group (HG, n=35, altitude: 2 808 m to 3 400 m). According to the diagnostic criteria of Lushan conference and Marshall (1995) commonly used on plain, and Lanzhou criteria drafted by the authors, three data analyzing models were set up to draw the receiver operating characteristic (ROC) curves, the Yordon Index and the optimum cutoff points of the parameters were calculated and the accuracy of the three respective diagnostic criteria was evaluated in predicting the outcome of ARDS/MODS. Multiple factors affecting the outcome of MODS were analyzed using the method of stepwise forward regress model. RESULTS: Following the increase in altitude, Lanzhou criteria was clearly superior to the other two criteria in the area of ROC, the sensitivity, the specificity, and also for the optimum cutoff points of MODS. Multi-variable regression analysis showed that the impacting factor of Lanzhou criteria was the highest (P<0.05). CONCLUSION: (1)Some parameters of the current diagnostic criteria of ARDS/MODS are not suitable in moderately high or high altitude areas. It is necessary to set up the diagnostic criteria of H-ARDS/MODS. (2)Some clinical characteristics might change in areas 1,500 m altitude or higher. The pathophysiological mechanism might be attributable to peculiar biologic reactions due to hypoxia stress reaction, and it is worth further study.

[Criteria suitable for diagnosis of acute respiratory distress syndrome/multiple organ dysfunction syndrome at moderately high altitude area].

OBJECTIVE: To compare the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plain, and to establish a more practical diagnostic criterion of H-ARDS/MODS. METHODS: Five hundred and five cases fulfilled the criteria for the diagnosis of ARDS/MODS were divided into three groups according to the altitude of their habitation: control group including inhabitants (<430 m) on plain (CG, n=113), moderate high altitude group 1 inhabitants at the altitude of 1,517 m (H1G, n=314), moderate high altitude group 2 inhabitants at the altitude of 2,261 m to 2,400 m (H2G, n=78). The ARDS/MODS scores of the three groups were made according to the diagnostic criteria of Lushan conference, Marshall(1995) and Lanzhou criteria drafted by the authors respectively to set up three data analyzing models, followed by plotting of receiver operating characteristic curves (ROC curve) and calculation of the Yordon Index and the optimum cutoff points of the parameters,in order to study the accuracy of the three diagnostic criteria in predicting the outcome of the patients suffering from ARDS/MODS. RESULTS: In CG group, the differences were not significant in area of ROC, the maximal Yordon Index, the optimum cutoff points and the sensitivity and the specificity for three criteria; but the differences were significant for the three criteria in H1G group. Further investigation in comparing the ROC values of lung, brain, heart and kidney, the Lanzhou criteria were more advantageous in the high altitude than the other criteria. CONCLUSION: (1)The current diagnostic criteria of ARDS/MODS are not suitable for the diagnosis of these syndromes in moderately high or high altitude areas. It is necessary to revise the diagnostic criteria of H-ARDS/MODS. (2)One thousand five hundred and seventeen meters in altitude might be considered to be an important borderline, above with the diagnostic criteria of ARDS/MODS for patients inhabiting on plain could not be suitably applied to those living above this level.

NDRG2 expression and mutation in human liver and pancreatic cancers.

AIM: To investigate the expression of NDRG2 and mutation of the entire coding region of NDRG2 in human liver and pancreatic cancers, and to further discuss the possible causes of NDRG2 distinct expression patterns. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze the expression of NDRG2 mRNA in 37 fresh cancer specimens (including 8 cases of pancreatic cancer and 29 cases of liver cancer) and adjacent normal tissues collected from clinical operation. In addition, mutation analysis of the whole coding region of NDRG2 in these cancers was examined by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). RESULTS: Compared with adjacent normal tissues, the expression levels of NDRG2 mRNA in corresponding cancer tissues reduced significantly (pancreatic cancer: 0.680+/-0.112 vs 2.089+/-0.214, P<0.01) (liver cancer: 0.894+/-0.098 vs 1.345+/-0.177, P<0.05). Using PCR-SSCP, the mutation of the whole coding region of NDRG2 was not found in those cancer tissues where the expression of NDRG2 mRNA reduced markedly. CONCLUSION: NDRG2 gene might express differently between normal tissues and cancer tissues, and might play an important role in the development of pancreatic cancer and liver cancer. Low expression of NDRG2 might be unrelated to the mutation of coding region of NDRG2.

[Vasorelaxing effect of idoxifene on human internal mammary arteries].

The purpose of this study was to investigate the vasorelaxing effect and mechanism of idoxifene (a new estrogen receptor modulator) on human internal mammary artery (HIMA). HIMA segments were harvested from men during coronary artery bypass grafting surgery. Patients with diabetes mellitus, hypercholesterolemia, hypertension, or smoking habit were excluded. The vasorelaxing effect of idoxifene on artery rings from HIMA with and without endothelium was measured by means of perfusion in vitro. Cumulative dose-response to idoxifene in the range of 0.01-10 micromol/L was observed in the presence and absence of NO synthase inhibitor L-NAME. It was also studied whether the vasodilation effect of idoxifene on HIMA was blocked by methylene blue (MB), an inhibitor of guanylate cyclase (GC). The results obtained from idoxifene were compared with those from 17beta-estradiol (E(2)). It was found that idoxifene caused a concentration-dependent relaxation on HIMA. The dose range was from 0.03 micromol/L (minimal vasodilatory concentration) to 3 mmol/L (maximal vasodilatory concentration). It was also found that the vasorelaxation effect of idoxifene on HIMA was dependent on endothelium. E(2) (0.1-100 micromol/L) also resulted in an endothelium-dependent vasorelaxation, but the vessels were 15-fold less sensitive to E(2) than to idoxifene in their vasorelaxation responses. The EC(50) for E(2) was 4.65+/-0.34 micromol/L, compared with 0.32+/-0.02 micromol/L for idoxifene. The mean maximal vasodilatory value of E(2) was 88.3+/-5.7%, compared with 88.6+/-7.2% for idoxifene. Pretreatment with L-NAME (100micromol/L) abolished idoxifene-induced vasodilation virtually by blocking nitric oxide production. The vasorelaxing effect of idoxifene disappeared in the presence of MB (10 micromol/L). These findings demonstrate that idoxifene results in an endothelium-dependent vasorelaxation of HIMA, like estrogen. The effect of idoxifene is more potent than that of traditional estrogen, and is possibly mediated by NO-GC-cGMP pathway.

[Study of diagnostic criteria of acute respiratory distress syndrome and multiple organ dysfunction syndrome at high altitude: revised draft of the diagnostic criteria of high acute respiratory distress syndrome drawn in Lanzhou conference].

OBJECTIVE: To compare the difference of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plains and reevaluate the practicality and feasibility of the diagnostic criteria of H-ARDS (Lanzhou conference, 1999). METHODS: Three hundred and sixty cases with relatively complete data were divided into three groups according to their originating altitude: control group on plains (CG, n=93), high altitude group 1 at the altitude of 1,517 m (H1G, n=223), high altitude group 2 at the altitude of 2,261-2,400 m (H2G, n=44). The ARDS/MODS scorings of the three groups were carried out according to the diagnostic criteria of Lushan Conference, Marshall (1995) and Lanzhou criteria drafted by the authors and the receiver operating characteristic curves (ROC curve) were made to predict the outcome of MODS. RESULTS: In CG group, the area of ROC, the susceptibility and specificity were 0.823, 0.833, 0.731, respectively according to Lushan criteria, which were better than those (0.815, 0.767, 0.763) according to Marshall criteria. Then in group H2G, the area of ROC, the susceptibility and specificity according to Lushan criteria were lower than those according to Marshall criteria: 0.855, 0.583, 0.969 vs 0.914, 1.000, 0.657. The optimum cutoff points of partial pressure of oxygen in artery (PaO(2))/fractional concentration of inspired oxygen (FiO(2)) were 198.32 mmHg, 131.50 mmHg and 97.58 mmHg in group CG, H1G and H2G. CONCLUSION: (1) There are significant differences between the diagnostic criteria of ARDS at high altitude and that on plains. The altitude of 1 517 m would be an important border line in diagnosing H-ARDS. (2) The drafted diagnostic criteria of ARDS at high altitude are feasible and practical in this region, but the range of the parameters is still wide, which need to be properly amended. (3) The changing tendency of the parameters of MODS at high altitude is different from that on plains, but the amount of sample needs to be accumulated further and the Lanzhou criteria needs to be perfected.