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Background & Aims Acute liver failure (ALF) is a life-threatening condition with limited treatment alternatives. ALF pathogenesis seemingly involves the complement system. However, no complement-targeted intervention has been clinically applied. In this study, we aimed to investigate the potential of Complement-5 (C5)-targeted ALF treatment. Methods ALF was induced in C5-knockout (KO, B10D2/oSn) mice and their wild-type (WT) counterparts (B10D2/nSn) through intraperitoneal lipopolysaccharide (LPS) and d -galactosamine (D-GalN) administration. Thereafter, monoclonal anti-C5 antibody (Ab) or control immunoglobulin was administered intravenously. Furthermore, a selective C5a-receptor (C5aR) antagonist was administered to WT mice to compare its efficacy with that of anti-C5-Ab-mediated total C5 inhibition. We clarified the therapeutic effect of delayed anti-C5-Ab administration after LPS/D-GalN challenge. We also assessed the efficacy of anti-C5-Ab in another ALF model, using concanavalin-A. Results Liver injury was evident 6 hours after LPS/D-GalN administration. C5-KO and anti-C5-Ab treatment significantly improved overall animal survival and significantly reduced serum transaminase and high-mobility group box-1 release with decreased histological tissue damage. This improvement was characterized by significantly reduced CD41+ platelet aggregation, maintained F4/80+ cells, and less infiltration of CD11+/Ly6-G+ cells with lower cytokine/chemokine expression. Furthermore, C5-KO and anti-C5-Ab downregulated tumor necrosis factor-α production by macrophages before inducing marked liver injury. Moreover, single-stranded-DNA cells and caspase activation were reduced, indicating significant attenuation of apoptosis. Anti-C5-Ab treatment protected the liver more effectively than the C5aR antagonist, and its delayed doses were hepatoprotective. In addition, anti-C5-Ab treatment was effective against concanavalin-A–induced ALF. Conclusions C5 inhibition effectively suppresses progression to ALF in mice models of fulminant hepatitis, serving as a new potential treatment strategy for ALF.

Lung metastasis of Triple-negative breast cancer (TNBC) causes severe breath-related events and poor prognosis. Ruyiping (RYP), a traditional Chinese medicine prescription, is used to treat breast cancer lung metastasis in clinical practice. This study was to explore the anti-lung-metastatic activities and mechanism of RYP extract by regulating macrophage polarization. The results showed that RYP can inhibit the viability and induce the apoptosis of TNBC cells. In in vitro experiments, RYP significantly inhibited the invasion and migration ability of TNBC cells promoted by M2, the subtype of macrophage which increased TNBC metastasis related genes. In in vivo experiments, RYP reduced the TNBC progression and lung metastasis. M2/M1 ration in the lung and M2 in the tumor was reduced by RYP, as well as M2 master regulator Stat6. Therefore, RYP extract may exhibit anti-lung metastasis function by reducing M2 in both tumor and lung through reducing Stat6.

Background Src, an oncoprotein that drives progression of head and neck squamous cell carcinoma (HNSCC), is commonly hyperactivated in this disease. Unfortunately, the clinical benefit of targeting Src is significantly dampened in HNSCC patients, because the cytotoxic effects of anti-Src therapy and tumor resistance to it are less predictable. Thus, understanding the mechanism of tumor resistance to Src inhibition and seeking a way to overcome it are warranted. Methods Dual drug-loaded nanoparticles (NPs) were developed to co-deliver Src inhibitor saracatinib (AZD0530) and AKT inhibitor capivasertib (AZD5363) into the same population of tumor cells. An orthotopic tongue tumor model was generated to evaluate the in vivo therapeutic effects. Cell growth was determined by CellTiter-Glo® Luminescent Cell Viability Kit, colony formation, and 3D culture, and tumor growth was determined by bioluminescence and tumor size. The molecular changes induced by the treatments were assessed by Western blotting and immunohistochemistry. Results Capivasertib inactivated the AKT-S6 signaling and re-sensitized saracatinib-resistant HNSCC cells to saracatinib. Combination of capivasertib with saracatinib suppressed HNSCC growth more efficiently than either drug alone. Cathepsin B-sensitive NPs for co-delivering saracatinib and capivasertib significantly improved the efficacy of tumor repression without increasing side effects, which were due to highly specific tumor-targeting drug delivery system and synergistic anticancer effects by co-inactivation of AKT and Src in HNSCC cells. Conclusions Addition of AKT blockade improves anti-HNSCC efficacy of anti-Src therapy, and co-delivery of capivasertib and saracatinib by tumor-targeting NPs has the potential to achieve better treatment outcomes than the free drug combination.

Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD.

The incidence rate of head and neck squamous cell carcinoma (HNSCC) has steadily increased over the past decade. However, treatment options for metastatic HNSCC are often limited and the 5‐year survival rate has remained static. Therefore, the development and assessment of more efficient but less toxic therapeutic strategies is an unmet need for treatment of more extensive HNSCC. Here, we report that CYT997, a novel microtubule‐disrupting agent, exerts strong activity in inhibiting HNSCC cell invasion and metastasis. The loss of invasion capacity by CYT997 was accompanied by an associated increase in cell adhesion and the reversal of epithelial‐mesenchymal transition (EMT). Increased expression of E‐cadherin protein and decreased expression of Vimentin protein became evident in HNSCC cells following CYT997 exposure, which were consistently observed in HNSCC xenografts from the mice receiving CYT997. Moreover, the capacity of invasive HNSCC cells to form pulmonary metastases was significantly blocked with CYT997 treatment, indicating that the diminishment of EMT traits contributes to CYT997‐suppressed metastasis. Intriguingly, CYT997 impaired intracellular ATP levels in HNSCC cells, at least in part, through its inhibitory effect on the mitochondrial protein IF1. The addition of ATP attenuated CYT997‐induced suppression of cell invasion, coupled with down‐regulation of E‐Cadherin and up‐regulation of Vimentin. These findings support a critical role of ATP levels in cell invasion and metastasis under the influence of CYT997. Collectively, our data unveil the mechanism involved in mediating CYT997 action, and provide preclinical rationale for possible clinical application of CYT997 as a novel therapeutic strategy against aggressive HNSCC.

OBJECTIVES The energy consumption process of cochlea and neural signal transduction along the auditory pathway are highly dependent on blood oxygen supply. At present, it is under debate on whether the obstructive sleep apnea syndrome (OSAS) would affect the auditory function since the patients suffer from low oxygen saturation. Moreover, it is difficult to detect the functional state of auditory in less severe stage of OSAS. Recently, speech-evoked auditory brainstem response (speech-ABR) has been reported to be a new electrophysiological tool in characterizing the auditory dysfunction. The aim of the present study is to evaluate the auditory processes in adult patients with mild and moderate OSAS by speech-ABR. METHODS An experimental group of 31 patients with mild to moderate OSAS, and a control group without OSAS diagnosed by apnea hypopnea index in polysomnogram were recruited. All participants underwent otologic examinations and tests of pure-tone audiogram, distortion product otoacoustic emissions, click-evoked auditory brainstem response (click-ABR) and speech-ABR, respectively. RESULTS The results of pure-tone audiogram, distortion product otoacoustic emissions, and click-ABR in OSAS group showed no significant differences compared with the control group (P>0.05). Speech-ABRs for OSAS participants and controls showed similar morphological waveforms and typical peak structures. There were significant group differences for the onset and offset transient peaks (P

The clinical application of human bone marrow mesenchymal stem cells (hBM-MSCs) has generated a great deal of interest because of their potential use in regenerative medicine and tissue engineering. However, safety concerns over hBM-MSCs limit their clinical application. In this study, we observed that hBM-MSC-conditioned medium (hBM-MSC-CM) promotes gastric cancer development via upregulation of c-Myc. Our results showed that c-Myc was upregulated in MGC-803 and BGC-823 cells after hBM-MSC-CM treatment. Moreover, we found that the c-Myc inhibitor JQ1 and c-Myc siRNA decreased the expression of c-Myc in hBM-MSC-CM-treated tumor cells in vitro. Additionally, hBM-MSC-CM enhanced the migration and glucose uptake of gastric cancer cells. In vivo studies showed that JQ1 inhibited hBM-MSC-CM-induced gastric cancer growth. These results indicated that hBM-MSC-CM induced gastric cancer growth via upregulation of c-Myc, which may be a potential risk factor and/or a therapeutic target for clinical applications.

In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO.

Background Although major improvements have been made in surgical management, chemotherapeutic, and radiotherapeutic of prostate cancer, many prostate cancers remain refractory to treatment with standard agents. Therefore, the identification of new molecular targets in cancer progression and development of novel therapeutic strategies to target them are very necessary for achieving better survival for patients with prostate cancer. Activation of small GTPases such as Ras and Arf1 is a critical component of the signaling pathways for most of the receptors shown to be upregulated in advanced prostate cancer. Methods The drug effects on cell proliferation were measured by CellTiter 96® AQueous One Solution Cell Proliferation Assay. The drug effects on cell migration and invasion were determined by Radius™ 24-well and Matrigel-coated Boyden chambers. The drug effects on apoptosis were assessed by FITC Annexin V Apoptosis Detection Kit with 7-AAD and Western blot with antibodies against cleaved PARP and Caspase 3. A NOD/SCID mouse model generated by subcutaneous injection was used to assess the in vivo drug efficacy in tumor growth. ERK activation and tumor cell proliferation in xenografts were examined by immunohistochemistry. Results We show that Exo2, a small-molecule inhibitor that reduces Arf1 activation, effectively suppresses prostate cancer cell proliferation by blocking ERK1/2 activation. Exo2 also has other effects, inhibiting migration and invasion of PCa cells and inducing apoptosis. The Ras inhibitor salirasib augments Exo2-induced cytotoxicity in prostate cancer cells partially by enhancing the suppression of ERK1/2 phosphorylation. In a xenograft mouse model of prostate cancer, Exo2 reduces prostate tumor burden and inhibits ERK1/2 activation at a dose of 20 mg/kg. Synergistic treatment of salirasib and Exo2 exhibits a superior inhibitory effect on prostate tumor growth compared with either drug alone, which may be attributed to the more efficient inhibition of ERK1/2 phosphorylation. Conclusion This study suggests that simultaneous blockade of Arf1 and Ras activation in prostate cancer cells is a potential targeted therapeutic strategy for preventing prostate cancer development. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0583-4) contains supplementary material, which is available to authorized users.

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

Background It is a matter of great importance in a donation after cardiac death to attenuate ischemia–reperfusion injury (IRI) related to the inevitable warm ischemic time. Methods Donor dogs were rendered cardiac-dead and left at room temperature. The dogs were allocated into 2 groups: the β-2 group ( n = 5) received an aerosolized β-2 adrenoreceptor agonist (procaterol, 350 μg) and ventilation with 100% oxygen for 60 minutes starting at 240 minutes after cardiac arrest, and the control group ( n = 6) received an aerosolized control solvent with the ventilation. Lungs were recovered 300 minutes after cardiac arrest. Recipient dogs underwent left single-lung transplantation to evaluate the functions of the left transplanted lung for 240 minutes after the reperfusion. Results Oxygenation and dynamic compliance were significantly higher in the β-2 group than in the control group. The β-2 group revealed significantly higher levels of cyclic adenosine monophosphate and high-energy phosphates in the donor lung after the inhalation than before it. Histologic findings revealed that the β-2 group had less edema and fewer inflammatory cells. Conclusion Our results suggest that β-2 adrenoreceptor agonist inhalation during the pre-procurement period may ameliorate IRI.

Summary Pediatric recipients of living-donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi-allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post-Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr-tol), but not in 50 intolerant patients (Gr-intol). The Gr-intol consisted of 24 patients with rejection (Gr-rej) and 26 with fibrosis of grafts (Gr-fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11–7.02, P = 0.03], was a positive independent predictor, whereas HLA-A mismatch (0.18, 0.03–0.91, P = 0.04) was a negative predictor. HLA-DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr-intol (4.9%) compared with Gr-tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr-Tol (P = 0.02). Although HLA-B mismatch (8.73, 1.09–70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA-A match and the later predominance of Tregs are factors associated with OT.

[Background.] One method of countering chronic lung donor shortages is the practice of donation after cardiac death (DCD). However, this technique inevitably leads to pulmonary dysfunction related to warm ischemia. One promising method of alleviating this problem is ventilation. However, it can rarely be initiated from the onset of cardiac arrest, particularly in uncontrolled DCD donors. We investigated the protective effect of the last 60 min of ventilation during a 240-min warm ischemic time. [Methods.] We rendered donor dogs cardiac dead and left them at room temperature. Six dogs received ventilation with 100% oxygen for 60 min starting at 180 min after cardiac arrest (ventilation group). Eight dogs received no ventilation. Lungs were harvested 240 min after cardiac arrest, then transplanted into recipient dogs. At 60 min after reperfusion, the right pulmonary artery was ligated, and the function of the left transplanted lung was evaluated. [Results.] In the ventilation group, all six animals survived for 240 min after reperfusion, whereas in the nonventilation group, only four of eight survived. The ventilation group demonstrated significantly better pulmonary oxygenation, shunt fraction, and wet-to-dry weight ratio. Furthermore, the ventilation group revealed significantly higher levels of high-energy phosphates in the lung tissues, fewer apoptotic cells, lower levels of tumor necrosis factor-α and interleukin-8 messenger RNA in the lung tissues, and lower levels of interleukin-6 messenger RNA in the serum. [Conclusion.] Our results suggest that ventilation during the late phase of the preprocurement period may ameliorate ischemia-reperfusion injury in DCD donors.

Outcome for highly immunogenic lung transplantation remains unsatisfactory despite the development of potent immunosuppressants. The poor outcome may be the result of a lack of minimally invasive methods to detect early rejection. There is emerging clinical evidence that, paradoxically, expression of forkhead box P3 (FOXP3, a specific marker for the regulatory T cells) is upregulated within rejecting grafts.Orthotopic lung transplantation was performed using miniature swine without immunosuppression. Rejection was monitored by chest radiography and open lung biopsy. Expressions levels of FOXP3, perforin, Fas-L and IP-10 mRNA were quantified in the peripheral blood. In addition, rescue immunosuppressive therapy (steroid plus tacrolimus) was administered on post-operative day (POD) 4 or 6.Early rejection was detected by open lung biopsy, but misdiagnosed by chest radiography on POD 4. Expression of FOXP3 in the peripheral blood reached its highest value as early as POD 4, followed by a decline. Such an increase of FOXP3 was not observed in recipients given high-dose tacrolimus. Neither perforin, Fas-L or IP-10 in the peripheral blood exhibited significant fluctuations in the early phase of rejection. Rescue immunosuppressive therapy from POD 4, when peak FOXP3 was seen, prolonged graft survival (27.2 days, versus 9.1 days without immunosuppression, p0.001), in contrast to POD 6, when rejection was suspected by chest radiography (11.5 days, p = not statistically significant [NS]).In a miniature swine lung transplantation model, the FOXP3 mRNA level in the peripheral blood was upregulated at an early phase of rejection. The clinical implication of this finding remains to be elucidated.

Loss of cell surface expression of CD127 on CD4(+)CD25(++) regulatory T-cells (Tregs) may be a useful marker to efficiently isolate Tregs. As FOXP3 was specifically used to identify Tregs, combining these two markers could give better identification for patient with operational tolerance (OT) after liver transplantation. To testify this mixed lymphocyte reaction (MLR), the function of circulating CD4(+)CD25(++)CD127(dim) cells (CD127(dim) cells) was examined in immunosuppression (IS)-free pediatric recipients after liver transplantation (LTx) (group operational tolerance: OT) (Gr-tol n=25) compared to recipients who could not stop IS due to clinically overt rejection (group intolerance) (Gr-intol n=18), recipients who were weaning IS (Gr-weaning n=11) and age-matched healthy volunteers (Gr-vol n=11). In addition, the frequencies of CD127(dim) cells vs CD4(+)CD25(++)CD127(dim)FOXP3(+) (CD127(dim)FOXP3(+)) cells were compared in these four groups by FACS analyses. Our results showed that The proliferation of CD4 cells to donor antigens was reduced compared to third-party antigens only in Gr-tol (P=0.022) but not in other groups (P=NS). Depletion of CD127(dim) cells resulted in a donor antigen-specific abrogation of this MLR hyporesponsiveness in Gr-tol (P

After lung transplantation, early detection of acute allograft rejection is important not only for timely and optimal treatment, but also for the prediction of chronic rejection which is a major cause of late death. Many biological and immunological approaches have been developed to detect acute rejection; however, it is not well known whether lung mechanics correlate with disease severity, especially with pathological rejection grade. In this study, we examined the relationship between lung mechanics and rejection grade development in a rat acute rejection model using the forced oscillation technique, which provides noninvasive assessment of lung function. To this end, we assessed lung resistance and elastance (RL and EL) from implanted left lung of these animals. The perivascular/interstitial component of rejection severity grade (A‐grade) was also quantified from histological images using tissue fraction (TF; tissue + cell infiltration area/total area). We found that TF, RL, and EL increased according to A‐grade. There was a strong positive correlation between EL at the lowest frequency (Elow; EL at 0.5 Hz) and TF (r2 = 0.930). Furthermore, the absolute difference between maximum value of EL (Emax) and Elow (Ehet; Emax − Elow) showed the strong relationship with standard deviation of TF (r2 = 0.709), and A‐grade (Spearman's correlation coefficients; rs = 0.964, P < 0.0001). Our results suggest that the dynamic elastance as well as its frequency dependence have the ability to predict A‐grade. These indexes should prove useful for noninvasive detection and monitoring the progression of disease in acute rejection., After lung transplantation, early detection of acute allograft rejection is important for both in timely treatment and prediction of chronic rejection which is a major cause of late death. We examined the relationship between lung mechanics and rejection grade development in a rat acute rejection model using the forced oscillation technique, which provides noninvasive assessment of lung function. Our results suggest that the dynamic elastance as well as its frequency dependence reflect the perivascular‐interstitial component of rejection severity grade (A‐grade), and this method should prove useful for noninvasive detection and monitoring the progression of disease in acute rejection.

Theoretical analyses and simulations of terahertz generation based on difference frequency generation in nonlinear crystal ZnTe are presented in this paper. Owing to the phase mismatching and crystal absorption, the crystal length has great influence on the spectral width and determines the central frequency of the terahertz radiation. The dependence of the temporal and spectral waveforms on the pump pulsewidth is also studied in this paper.

Background. CD4 + CD25 ++ CD45RA + cells (naive regulatory T cells [naive-Tregs]) have been identified as a functionally premature form of CD4 + CD25 +++ CD45RA - cells (conventional-Tregs). However, their contribution to transplant tolerance remains to be elucidated. Method. We examined the frequency and the function of conventional and naive-Tregs in the peripheral blood derived from operationally tolerant patients after pediatric living-donor liver transplant (Gr-tol). The data were compared with those of patients who were unable to be weaned off immunosuppression due to rejection (group-intolerance [Gr-intol]), patients in the process of weaning immunosuppression (Gr-weaning) and healthy volunteers (group-healthy volunteers [Gr-vol]). Results. In Gr-tol, the frequency of conventional-Tregs was significantly higher than that in Gr-vol and tended to be higher than that in Gr-intol. The frequency of naive-Tregs was significantly decreased in Gr-intol versus those in Gr-tol, -weaning, and -vol. In mixed lymphocyte reactions, donor-specific hyporesponsiveness of CD4 + cells was observed only in Gr-tol but not in the other groups. Depletion of conventional or naive-Tregs from CD4 + cells demonstrated that the suppressive properties of donor antigen-reactive conventional and naive-Tregs were upregulated compared with those of third-party antigen-reactive conventional and naive-Tregs in Gr-tol only. Conclusions. This is the first report providing detailed evidence that donor-specific naive-Tregs were generated and their suppressive properties were upregulated in the peripheral blood of tolerant patients, whereas their frequency was downregulated in intolerant patients. Therefore, we speculate that not only conventional-Tregs play a role in Tx tolerance but also the role of naive-Tregs is critical.

We presented a design of the zone plate with continuous phase with Polytetrafluoroethylene (PTFE) based on scalar diffraction theory. Diffraction fields of the zone plate with continuous phase and the phase-correcting Fresnel zone plate with incidence of uniform plane wave were analyzed and compared. The effects of the focal length and diameter of the zone plate with continuous phase on the diffraction field were discussed. The simulations of intensity distribution on the focal plane and the optic axis based on Rayleigh-Sommerfeld diffraction formula were completed using Matlab. The results indicate that the zone plate with continuous phase performs better than the phase-correcting Fresnel zone plate. The intensity on the focus of the zone plate with continuous phase is 1.17, 1.35, 2.62 times stronger than that on 8-level, 4-level, 2-level phase-correcting Fresnel zone plate's respectively. The fabrication process might give rise to a phase error, such as groove depth error, surface roughness. The effects of the phase errors on the performance of the zone plate were discussed.

Background Operational tolerance is defined as long-term acceptance of a transplanted organ after complete cessation of immunosuppression (IS), but may not always protect against antigen-dependent changes in graft morphology. Method IS free patients after living-donor liver transplantation (LDLT) underwent protocol biopsy (tolerance group [Gr-Tol]) and were evaluated for rejection and fibrosis. The degree of fibrosis was compared with those in the patients on maintenance IS group (Gr-IS) and the base line normal liver group (Gr-BS). When bridging fibrosis or progression of fibrosis was observed, IS was reintroduced or increased in Gr-Tol or in the patients in the weaning process. Results Neither acute nor chronic rejection was observed. The degree of fibrosis, however, was significantly greater in Gr-Tol than those in Gr-IS and Gr-BS. In Gr-Tol, the number of graft infiltrating FOXP3 cells was significantly increased, the interval between LDLT and biopsy plus the donor age was significantly longer, and recipient age at LDLT was significantly younger, compared with those in Gr-IS. However, none of these three parameters correlated with the degree of fibrosis. In 7 of 11 patients in whom IS was reintroduced or increased, the improvement of fibrosis was observed by the subsequent biopsy. Conclusion Grafts of operationally tolerant patients after LDLT did not exhibit acute or chronic rejection, but they exhibited fibrosis. It remains elusive whether fibrosis observed in tolerant grafts is antigen dependent. The finding that after [corrected] the reintroduction or the increase of IS fibrosis was improved supported the possibility that fibrosis in operationally tolerant patients was antigen dependent.

Modern enterprise manages indexes more refined and systematically. This paper reviews common construction and function of data warehouse on huge Iron & Steel enterprise and gives an example of Enterprise's index. This example explains the process of building subject data set and computing and analyzing indexes by models and methods in data warehouse platform. It is proved that using the results of the analysis by multi-way display, the enterprise's requirement can be met, and it can improve efficiency of production.

Air tends to accumulate at the vertex or the inflexion place of the pipeline in pressured water supply system. Air chambers will lead to the pressure losing. Research of the air chamber’s influence will contribute to a more complete and accurate hydraulic calculation. This paper analyzed the pressure-falling phenomenon caused by air chamber in quantificational, deduced two calculation formulas for pressure loss in static state and dynamic state, and discussed application of the formulas in especial states. The research indicate that the water head loss equals height difference between the front and back end of an air chamber, and it is a solution of a quartic equation of one variable in steady-state flow.

This paper firstly reviews common construction of information system of iron & steel enterprise, and then detailedly introduces five-layer structure of data warehouse. It is made of data source layer, operation data storage layer, subject data set layer, data analysis layer and data display layer. Among all, the concept and building process of subject data set and the characteristics of various models in data analysis layer are explained detailedly. Lastly this paper gives an analysis example of important quality index of rolling coil which introduces the process of selecting data source, building subject data set, analyzing data by calling methods and models in data analysis layer. It is proved that by building data warehouse system, it can improve efficiency of production and support enterprise's decision.

The control of warm ischemia-reperfusion injury is crucial in managing donors after cardiac death for lung transplantation. We focused on transalveolar administration as a drug-delivery route for such donors. Milrinone is a phosphodiesterase 3 inhibitor that inhibits the breakdown of cyclic adenosine monophosphate and selectively relaxes smooth muscle. We hypothesized that nebulized milrinone would mitigate warm ischemia-reperfusion injury of lung.This study was conducted with an isolated rat lung perfusion model. Lungs were excised, exposed to 55-minute ischemia at 37 degrees C, and reperfused for 60 minutes. During ischemia, nebulized milrinone (n = 6) or saline (n = 6) was inhaled. Lungs were continuously perfused without ischemia as a sham group (n = 6). Airway resistance, pulmonary vascular resistance, pulmonary compliance, weight gain and blood gas were measured. Adenine nucleotide levels and apoptosis were investigated in the reperfused lungs.Milrinone nebulization decreased post-ischemic pulmonary vascular resistance (0.98 +/- 0.05 and 1.74 +/- 0.17 cm H(2)O/ml.min at 60 minutes of reperfusion in the milrinone and control groups, respectively [p0.01]). It did not alter cyclic adenosine monophosphate levels, but it did elevate adenosine triphosphate levels (9.87 +/- 0.38 and 6.91 +/- 0.45 in the milrinone and control groups, respectively [p0.01]) and suppressed apoptosis (3.83 +/- 0.91 and 46.17 +/- 3.39 of mean apoptotic cell numbers in the milrinone and control groups, respectively [p0.01]).Milrinone nebulization decreased post-ischemic pulmonary vascular resistance, elevated adenosine triphosphate levels, and suppressed apoptosis. Nebulized milrinone has some protective effects against warm ischemia.

This paper describes efforts at monitoring microfloor vibrations in a newly-constructed research building. This building is intended to house a variety of delicate precision scientific instruments with performances that are deleteriously affected by even small floor vibrations. The building is five stories with welded steel construction. Upon completion of the construction, the initial occupants anecdotally complained of excessive floor vibrations. This resulted in an effort to measure the vibrations and to reduce them at their sources, including the mechanical systems for the building. The measurements are compared with industry standards and with measurements taken at nearby reinforced concrete buildings. The success of efforts at reducing the vibrations due to the mechanical systems of the building are also assessed.

AIM: To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery. METHODS: We describe the surgical procedures for our rat OLT model, and determined the operator learning curves. The various factors that contributed to successful surgery were determined. The most important surgical factors were evaluated between successful and unsuccessful surgeries. RESULTS: Learning curve data indicated that 50 cases were required for operator training to start a study. Operative time, blood loss, warm ischemic time, anhepatic phase, unstable systemic hemodynamic state, and body temperature after surgery significantly affected surgery success by univariate analysis, while the anhepatic phase was the most critical factor for success by multivariate analysis. CONCLUSION: OLT in rats is the only liver transplantation model that provides clinically relevant and reliable results. Shortened anhepatic phase is key to success in this model.

Purpose: Supercooling is defined as a non-freezing state of liquid below freezing temperature. Stable supercooling at the temperature between 0°C to –10°C is achieved in a newly developed refrigerator with a power voltage of 3,000 V. We hypothesized that supercooling would reduce metabolism of organ grafts and lungs preserved in supercooling would have better physiological function than in the clinically standard storage at 4°C. Methods and Materials: We investigated in a previously published isolated rat lung perfusion model, in which physiological parameters such as tidal volume, arterial oxygen tension, and lung weight were measured. The heart-lung block was preserved for 17 hr and subsequently reperfused for 60 minutes. All animals were divided into three groups. In the supercoolng group (n 7), non-freezing preservation at -2°C was kept in a supercooling refrigerator. In the control group (n 7), the ordinary hypothermic preservation was maintained at 4°C. In the sham group (n 7), after harvesting lungs were continuously perfused without hypothermic preservation. Results: Two animals in the control group were excluded from the following analysis because of severe lung edema within 12 minutes of reperfusion. Oxygen tensions at 60 minutes of reperfusion were 101.8 2.6 in the supercooling, 58.6 10.8 in the control, and 104.4 1.9 in the fresh (mmHg). At 60 minutes, tidal volumes were 2.0 0.1 in the supercooing, 1.0 0.3 in the control, and 2.2 0.1 in the fresh (mL). The lung weight gains during the 60 minutes were 1248 56, 2983 543, and 693 69, in supercooling, in control and in fresh, respectively (mg). Throughout the experiment, oxygen tensions and tidal volumes in the supercooling and the fresh were significantly higher than the control group(p 0.001, p 0.05, respectively), and the lung weight gains in the supercooling and the fresh were significantly lower than the control (p 0.001). Conclusions: Supercooling demonstrated the superiority in hypothermic preservation of rat lungs to the standard storage of 4°C in an isolated rat lung perfusion model.

Purpose: A method to compensate for the donor shortage could be the utilization of donation after cardiac death (DCD). However, the control of warm ischemia-reperfusion injury is crucial in manipulating DCD donors. Nebulization is a simple and feasible drug delivery route after cardiac death. Here we investigated the protective effect of nebulized milrinone, a phosphodiesterase III inhibitor, on pulmonary warm ischemia-reperfusion injury. Methods and Materials: We used an isolated rat lung perfusion model. The heart-lung block was excised with cannulation of the pulmonary artery and vein, exposed to 55 minutes of ischemia at 37C and reperfused for 60 minutes. All animals were divided into two groups. In the milrinone group (n 6), milrinone was nebulized for 10 minutes just during ischemia. In the control group (n 6), 0.9% saline was nebulized in the same timing. Lung tissue adenine nucleotide and cAMP levels were measured. The apoptosis of lung tissues were quantitatively evaluated by using the TUNEL assay. Results: Throughout the reperfusion period, the pulmonary vascular resistance in the milrinone group was significantly lower than that in the control group (p 0.01). On the other parameters such as pulmonary shunt fraction, dynamic airway resistance and weight gain, milrinone group also seemed to be better compared to the control group, but there were no significant differences between the groups. Lung tissue ATP levels at the end of reperfusion were 9.87 0.38 and 6.91 0.45 in the milrinone group and control group, respectively (nmol/mg dry weight, p 0.01). However, regarding lung tissue cAMP levels, there was no significant difference between the two groups. The mean TUNEL-positive cell numbers were 69.0 3.4 and 3.8 0.9 in the control group and milrinone group, respectively (p 0.01). Conclusions: We confirmed that milrinone nebulization during warm ischemia alleviated the lungs against warm ischemia-reperfusion injury. Our data showed that milrinone nebulization could be an effective method after cardiac arrest in lung transplantation from DCD donors.