Pharmacokinetics and safety of a new generic lurasidone: a phase I bioequivalence study in healthy Chinese subjects.

Latuda® is a novel antipsychotic drug for schizophrenia and bipolar depression. A bioequivalence trial was performed to investigate the bioequivalence of Latuda® and its generic drug lurasidone. Two independent trials were carried out, each involving 28 subjects. In the fasting trial, subjects were randomly assigned to two groups (1:1 ratio), receiving either 40 mg of generic lurasidone or Latuda®. After a 7-day washout period, subjects entered the second period with a crossover administration of 40 mg of generic lurasidone or Latuda®. The postprandial study design was similar to that of the fasting study. In the fasting study, the pharmacokinetic (PK) parameter values of generic lurasidone and Latuda® were as follows: the Cmax was 28.84 ± 19.34 ng/ml and 28.22 ± 21.19 ng/ml, respectively; the AUC0-t was 121.39 ± 58.47 h*ng/ml and 118.35 ± 52.24 h*ng/ml, respectively; and the AUC0-∞ was 129.63 ± 63.26 h*ng/ml and 126.59 ± 57.99 h*ng/ml, respectively. The primary pharmacokinetic parameter, Cmax, was assessed for equivalence using reference-scaled average bioequivalence (RSABE), while other parameters (AUC0-t, AUC0-∞) were evaluated using average bioequivalence (ABE). The results indicate that both Cmax and AUC meet the equivalence criteria. In the postprandial study, the PK values of generic lurasidone and Latuda® were as follows: the Cmax was 74.89 ± 32.06 ng/ml and 83.51 ± 33.52 ng/ml, respectively; the AUC0-t was 274.77 ± 103.05 h*ng/ml and 289.26 ± 95.25 h*ng/ml, respectively; and the AUC0-∞ was 302.44 ± 121.60 h*ng/ml and 316.32 ± 109.04 h*ng/ml, respectively. The primary pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) were assessed for equivalence using ABE, and both met the equivalence criteria. In the study, lurasidone and Latuda® both exhibited acceptable safety and tolerability. The results displayed that lurasidone and Latuda® were bioequivalent and safe in healthy Chinese participants. Clinical Trial Registry: This trial is registered at chinadrugtrials.org.cn (no.: CTR20191717, date: 2019.08.29).

Unlocking the Potential of A-Site Ca-Doped LaCo0.2Fe0.8O3-δ: A Redox-Stable Cathode Material Enabling High Current Density in Direct CO2 Electrolysis.

Massive carbon dioxide (CO2) emission from recent human industrialization has affected the global ecosystem and raised great concern for environmental sustainability. The solid oxide electrolysis cell (SOEC) is a promising energy conversion device capable of efficiently converting CO2 into valuable chemicals using renewable energy sources. However, Sr-containing cathode materials face the challenge of Sr carbonation during CO2 electrolysis, which greatly affects the energy conversion efficiency and long-term stability. Thus, A-site Ca-doped La1-xCaxCo0.2Fe0.8O3-δ (0.2 ≤ x ≤ 0.6) oxides are developed for direct CO2 conversion to carbon monoxide (CO) in an intermediate-temperature SOEC (IT-SOEC). With a polarization resistance as low as 0.18 Ω cm2 in pure CO2 atmosphere, a remarkable current density of 2.24 A cm-2 was achieved at 1.5 V with La0.6Ca0.4Co0.2Fe0.8O3-δ (LCCF64) as the cathode in La0.8Sr0.2Ga0.83Mg0.17O3-δ (LSGM) electrolyte (300 µm) supported electrolysis cells using La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) as the air electrode at 800 °C. Furthermore, symmetrical cells with LCCF64 as the electrodes also show promising electrolysis performance of 1.78 A cm-2 at 1.5 V at 800 °C. In addition, stable cell performance has been achieved on direct CO2 electrolysis at an applied constant current of 0.5 A cm-2 at 800 °C. The easily removable carbonate intermediate produced during direct CO2 electrolysis makes LCCF64 a promising regenerable cathode. The outstanding electrocatalytic performance of the LCCF64 cathode is ascribed to the highly active and stable metal/perovskite interfaces that resulted from the in situ exsolved Co/CoFe nanoparticles and the additional oxygen vacancies originated from the Ca2Fe2O5 phase synergistically providing active sites for CO2 adsorption and electrolysis. This study offers a novel approach to design catalysts with high performance for direct CO2 electrolysis.

Comparing the bioequivalence and safety of liraglutide in healthy Chinese subjects: an open, single-dose, randomized, repeated, two-sequence, two-cycle phase I clinical trial.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone. Liraglutide, a GLP-1 receptor agonist, can lower blood sugar by increasing insulin production and inhibiting the production of glucagon. This study researched the bioequivalence and safety of the test and reference drugs in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: Subjects (N = 28) were randomly divided into group A and group B at a ratio of 1:1 for a two-cycle cross-over study. There was single dose per cycle with subcutaneous injection of the test and reference drugs, respectively. The washout was set at 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. RESULTS: The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for the test and reference drugs were 107.11%, 106.56%, 106.09%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both had good safety in this study. CONCLUSION: The study shows that the two drugs had similar bioequivalence and safety. CLINICAL TRIAL REGISTRATION: DCTR: CTR20190914; ClinicalTrials.gov: NCT05029076.

Pharmacokinetics and safety of dasatinib and its generic: a phase I bioequivalence study in healthy Chinese subjects.

BACKGROUND: Dasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. RESEARCH DESIGN & METHODS: We designed a clinical study to demonstrate that the dasatinib tablet (YiNiShu®) (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Dasatinib (Bristol Myers Squibb) were bioequivalent under fasting and fed conditions. The whole study was structured into the fasting trial and the postprandial trial. Each period, subjects were given 50 mg dasatinib or its generic. The RSABE (reference scale average bioequivalence) and ABE (average bioequivalence) methods were employed to assess bioequivalence by pharmacokinetics (PK) parameters for a highly variable drug. RESULTS: 32 and 24 eligible volunteers were enrolled in the fasting and postprandial trials, respectively. In the fasting trial, the RSABE method was performed, and point estimates of Cmax, AUC0-t, and AUC0-∞ met the bioequivalence criteria. In the postprandial trial, the ABE method was performed, and the 90% CI of the geometric mean ratio (GMR) for PK parameters met the requirements of bioequivalence standards. CONCLUSION: The results proved that the PK parameters of the two drugs were similar and bioequivalent, indicating that both drugs had a good safety profile. CLINICAL TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (Number: NCT05640804) and Drug Clinical Trial Registration and Information Disclosure Platform (Number: CTR20181708).

A randomized, crossover, phase I clinical study to evaluate bioequivalence and safety of tofacitinib and Xeljanz® in Chinese healthy subjects.

OBJECTIVE: Tofacitinib is an oral Janus kinase (JAK) inhibitor that has been marketed and approved in the USA for the clinical treatment of rheumatoid arthritis, psoriasis and other inflammatory and autoimmune diseases. A phase I clinical trial was conducted to compare the bioequivalence and safety of tofacitinib (Chia Tai Tianqing Pharmaceutical Group Co., Ltd.) and Xeljanz® (Pfizer Inc.) in healthy Chinese subjects, providing basis for the clinical application of tofacitinib. METHODS: Healthy Chinese subjects (N = 32) were randomly assigned to two groups at a 1:1 ratio. Subjects orally took 5 mg tofacitinib or Xeljanz® per cycle in random sequence. Blood samples were collected at 15 sampling points per cycle, and plasma drug concentrations of tofacitinib or Xeljanz® were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and statistical analysis for the pharmacokinetic (PK) parameters. Subjects' physical indicators were monitored during the whole process to evaluate drug safety. RESULTS: The adjusted geometric mean ratios (GMRs) of the peak concentration (Cmax), area under the curve (AUC) from time zero to the last measurable concentration (AUC0-t) and AUC from time zero to observed infinity (AUC0-∞) were all within the range of 80-125%. The other PK parameter values were similar. The above values were all meeting the bioequivalence criteria with well safety. CONCLUSION: The pharmacokinetic parameters and safety profile of tofacitinib were similar to those of Xeljanz® in healthy Chinese subjects. Therefore, tofacitinib can be considered bioequivalent to Xeljanz®, and the findings of this trial will promote the clinical application of tofacitinib.

A randomized, open-label, single-dose, two-cycle crossover study to evaluate the bioequivalence and safety of lenvatinib and Lenvima® in Chinese healthy subjects.

BACKGROUND: Lenvatinib is a tyrosine kinase receptor inhibitor that inhibits vascular and endothelial growth factor receptor kinase activity. This study evaluated the bioequivalence and safety of lenvatinib with Lenvima® . RESEARCH DESIGN AND METHODS: The fasting and postprandial groups were two independent trials. Subjects were randomly divided into two sequences at a ratio of 1:1 for two-cycle crossover administration. Subjects took 10 mg lenvatinib or Lenvima® once per cycle. The wash-out period was 14 days. Detected the plasma drug concentrations and assessed the bioequivalence of two drugs. Besides, we evaluated the safety of the drugs throughout the trial. RESULTS: In the fasting state, the GMRs of Cmax, AUC0-t, and AUC0-∞ were 99.89%, 102.98% and 103.19%, respectively. The 90% CIs were all within 80%-125%. In the postprandial state, the GMRs of Cmax, AUC0-t, and AUC0-∞ were 98.96%, 94.25% and 95.27%, respectively. The 90% CIs were all within 80%-125%. All results met the bioequivalence criteria. Both drugs had good safety and tolerance in this trial. CONCLUSION: This study showed that lenvatinib and Lenvima® had similar bioequivalence and safety in healthy Chinese subjects under fasting and postprandial conditions. CLINICAL TRIAL REGISTRATION: This trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html # CTR20191172).

A randomized, double-blind, single-dose, single-center, parallel phase I clinical study comparing the pharmacokinetics, immunogenicity, safety, and tolerance of pertuzumab injection and Perjeta® in healthy Chinese male subjects.

BACKGROUND: Perjeta® is a recombinant, humanized monoclonal antibody that has been marketed and approved for the targeted therapy of human epidermal growth factor receptor (HER2) positive breast cancer in the United States. This study compared the bioequivalence, immunogenicity, and safety of pertuzumab injection (a biosimilar of Perjeta® produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Perjeta® (produced by Roche Pharma AG) in healthy Chinese males. RESEARCH DESIGN AND METHODS: Healthy Chinese male subjects (N = 87) were randomly given intravenous injection of 5 mg/kg pertuzumab or Perjeta® at a 1:1 ratio. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay, and primary pharmacokinetic parameters were statistically analyzed. We detected the levels of anti-drug antibody (ADA) and neutralizing antibody (nAb) to evaluate drug immunogenicity and safety of the drugs throughout the study. RESULTS: The geometric mean ratios of AUC0-t, Cmax, and AUC0-∞ for pertuzumab and Perjeta® were 100.42%, 96.71%, and 101.47%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. The levels of ADA and nAb were similar. In addition, both had good safety in the study. CONCLUSION: The study shows that pertuzumab injection and Perjeta® had similar bioequivalence, immunogenicity, and safety.

Blood neurofilament light chain in Parkinson disease and atypical parkinsonisms: A protocol for systematic review and meta-analysis.

BACKGROUND: Neurofilament light chain (NfL), an index of neuroaxonal injury, is a promising diagnostic and prognostic fluid biomarker with high translational value in many neurodegenerative disorders. Blood NfL measurement has been an exciting and active field of research in idiopathic Parkinson disease (PD) and atypical parkinsonisms. However, blood NfL levels in these parkinsonisms from existing literature were inconsistent. No comprehensive meta-analysis has ever been conducted. METHODS: Three major biomedical electronic databases PubMed, Embase, and Web of Science were comprehensively searched from inception to July 10, 2020. This protocol will be prepared based on the guidelines recommended by the statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Original observational studies that measured blood (serum/plasma) NfL concentrations in patients with parkinsonisms (multiple system atrophy [MSA], progressive supranuclear palsy [PSP], corticobasal syndrome [CBS], and dementia with Lewy bodies [DLB]), and healthy controls (HCs) will be included. Quality assessment of the included studies will be performed using the Newcastle Ottawa Scale (NOS). Meta-analyses will be conducted using the STATA software version 13.0. The standardized mean differences as the measure of effect size and 95% confidence intervals were calculated for each comparison of blood NfL levels. Heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be carried out to test the robustness of the results. RESULTS: The meta-analysis will obtain the effect sizes of blood NfL levels in the following comparisons: PD versus HC, MSA versus HC, PSP versus HC, CBS versus HC, DLB versus HC, MSA versus PD, PSP versus PD, CBS versus PD, and DLB versus PD. CONCLUSIONS: The present meta-analysis will provide the quantitative evidence of NfL levels in idiopathic PD and atypical parkinsonisms, hoping to facilitate differential diagnoses in clinical practice. REGISTRATION NUMBER: INPLASY202070091.

Cerebrospinal fluid and blood levels of neurofilament light chain in Parkinson disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Parkinson disease (PD) is a common neurodegenerative disorder. Elevations of neurofilament light chain (NfL) concentrations in the cerebrospinal fluid (CSF) and blood are a marker of neuronal/axonal injury and degeneration. However, CSF and blood NfL alterations in patients with PD from existing studies remain inconclusive. To better understand these conflicting data, we will conduct a meta-analysis. METHODS: We will comprehensively search PubMed, Embase, and Web of Science databases from each database's inception to 7th June, 2020. This protocol will conform to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. We will only include original studies published in English that evaluated differences of NfL concentrations in the CSF or blood between idiopathic PD patients and healthy controls. The Newcastle-Ottawa Scale will be used to evaluate the quality of the included studies. Meta-analyses will be carried out using the STATA software version 13.0. Between-group difference of NfL concentrations in the CSF and blood will be expressed as the weighted standardized mean difference. A random-effects model will be used. Supplementary analyses, such as heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be performed. RESULTS: The meta-analysis will provide the differences of NfL concentrations in the CSF and blood between patients with PD and healthy controls and will show the magnitudes of their effect sizes. CONCLUSIONS: This meta-analysis will provide the evidence of NfL concentrations in the CSF and blood in PD and we hope that our study has an important impact on clinical practice. REGISTRATION NUMBER: INPLASY202060025.

Inflammatory cytokine levels in multiple system atrophy: A protocol for systematic review and meta-analysis.

BACKGROUND: Multiple system atrophy (MSA) is a fatal neurodegenerative disease that progresses very rapidly and has a poor prognosis. Some studies indicate that the level of inflammatory cytokines may be related to MSA. However, no consistent conclusion has been drawn yet. The purpose of our research is to perform a meta-analysis to investigate whether the level of inflammatory cytokines is altered in MSA. METHODS: Case-control studies on inflammatory cytokine levels in MSA will be searched in the following 3 databases: PubMed, Embase, and Web of Science from the database start time to March 17, 2020. Two independent authors will conduct research selection, data extraction, and quality evaluation. Data synthesis, subgroup analysis, sensitivity analysis, and the meta-analysis will be performed using Stata15.0 software. RESULTS: This study will provide a comprehensive review of all studies on inflammatory cytokine levels in MSA. CONCLUSION: To the best of our knowledge, this study will be the first meta-analysis that provides the quantitative evidence of inflammatory cytokine levels in MSA. REGISTRATION NUMBER: INPLASY202060034.

Redox-Reversible Electrode Material for Direct Hydrocarbon Solid Oxide Fuel Cells.

Solid oxide fuel cells (SOFCs) can directly operate on hydrocarbon fuels such as natural gas; however, the widely used nickel-based anodes face grand challenges such as coking, sulfur poisoning, and redox instability. We report a novel double perovskite oxide Sr2Co0.4Fe1.2Mo0.4O6-δ (SCFM) that possesses excellent redox reversibility and can be used as both the cathode and the anode. When heat-treated at 900 °C in a reducing environment, double perovskite phase SCFM transforms into a composite of the Ruddlesden-Popper structured oxide Sr3Co0.1Fe1.3Mo0.6O7-δ (RP-SCFM) with the Co-Fe alloy nanoparticles homogeneously distributed on the surface of RP-SCFM. At 900 °C in an oxidizing atmosphere, the composite transforms back into the double perovskite phase SCFM. The excellent oxygen reduction reaction catalytic activity and mixed ionic-electronic conductivity make SCFM an excellent cathode material for SOFCs. When SCFM is used as the anode, excellent performance and stability are achieved upon either direct oxidation of methane as a fuel or operation with sulfur-containing fuels. The excellent redox reversibility coupled with outstanding electrical and catalytic properties manifested by SCFM will enable a broad application in energy conversion applications.

Clinical Utility of the Inflammatory Factors Combined With Lipid Markers in the Diagnostic and Prognostic Assessment of Ischemic Stroke: Based on Logistic Regression Models.

BACKGROUND: In this study, we developed novel logistic regression models for the diagnostic and prognostic assessment of ischemic stroke. METHODS: A total of 288 ischemic stroke patients and 300 controls admitted to The First Affiliated Hospital of Soochow University were included in the testing group. Two validation groups from The Affiliated Kunshan Hospital of Jiangsu University and The Second Affiliated Hospital of Soochow University were included to assess our novel assessment models. RESULTS: Results from the testing group indicated that the diagnostic assessment model for ischemic stroke prediction was: Logit(P) = 437.116 - 87.329 (Hypertension) - 89.700 (Smoking history) - 87.427 (Family history of ischemic stroke) - .090 (high-density lipoprotein cholesterol [HDL-C]) - 1.984 (low-density lipoprotein cholesterol [LDL-C]) - 17.005 (Lp(a)) - 15.486 (Apo A/Apo B), and the final prognostic assessment model of ischemic stroke was: Logit(P) = 458.437-92.343 (Hypertension) - 89.763 (Smoking history) + .251 (NLR) - .088 (HDL-C) - 1.994 (LDL-C) - 2.883 (hs-CRP) - .058 (IL-6) - 6.356 (TNF-α) - 16.485 (Lp(a)) - 17.658 (Apo A/Apo B). In the validation groups, our novel diagnostic assessment model showed good identification (with 87.5% sensitivity and 84.2% specificity in The Affiliated Kunshan Hospital of Jiangsu University, with 85.5% sensitivity and 89.0% specificity in The Second Affiliated Hospital of Soochow University). Moreover, our novel prognostic assessment model has a high value in identifying poor prognosis patients in the validation groups from The Affiliated Kunshan Hospital of Jiangsu University (χ2 = 8.461, P = .004), and The Second Affiliated Hospital of Soochow University (χ2 = 7.844, P = .005). CONCLUSIONS: The diagnostic and prognostic assessment models we have established are of great value in the diagnosis and prognostic evaluation of ischemic stroke.

Selection of piperacillin/tazobactam infusion mode guided by SOFA score in cancer patients with hospital-acquired pneumonia: a randomized controlled study.

BACKGROUND: This study aimed to select piperacillin/tazobactam (TZP) infusion mode guided by Sequential Organ Failure Assessment (SOFA) score in cancer patients with hospital-acquired pneumonia (HAP) postoperation. PATIENTS AND METHODS: A total of 120 cancer patients with postoperative HAP were divided into two groups: improved administration group (L group) and conventional treatment group (Con group). The Con group received traditional infusion of TZP and the L group received it as prolonged infusion. Blood drug concentration was detected at different time points. Based on the SOFA cut-off value of 9, the patients were regrouped into M (mild) and S (severe) groups. RESULTS: Percent time that the free drug concentrations remain above the minimum inhibitory concentration (%fT>MIC) was longer than 5 h in L group, but <4 h in Con group. Administration method (p=0.033, OX value 2.796, B value 1.028, 95% CI: 0.855-8.934) and SOFA score (p=0.038, OX value 0.080, B value -2.522, 95% CI: 0.007-0.874) were independent predictors of patient survival. In the S group, compared to conventional treatment, prolonged infusion mode resulted in shorter days of antibiotic use and shorter ventilator time, and achieved longer survival, better clinical efficacy, and lower 28-day mortality rate. CONCLUSION: For cancer patients with SOFA score ≥9, prolonged infusion of TZP could benefit the patients and obtain better clinical efficacy.

New, Efficient, and Reliable Air Electrode Material for Proton-Conducting Reversible Solid Oxide Cells.

Driven by the demand to minimize fluctuation in common renewable energies, reversible solid oxide cells (RSOCs) have drawn increasing attention for they can operate either as fuel cells to produce electricity or as electrolysis cells to store electricity. Unfortunately, development of proton-conducting RSOCs (P-RSOCs) faces a major challenge of poor reliability because of the high content of steam involved in air electrode reactions, which could seriously decay the lifetime of air electrode materials. In this work, a very stable and efficient air electrode, SrEu2Fe1.8Co0.2O7-δ (SEFC) with layer structure, is designed and deployed in P-RSOCs. X-ray diffraction analysis and High-angle annular dark-filed scanning transmission electron microscopy images of SEFC reveal that Sr atoms occupy the center of perovskite slabs, whereas Eu atoms arrange orderly in the rock-salt layer. Such a special structure of SEFC largely depresses its Lewis basicity and therefore its reactivity with steam. Applying the SEFC air electrode, our button switches smoothly between both fuel cell and electrolysis cell (EC) modes with no obvious degradation over a 135 h long-term test under wet H2 (∼3% H2O) and 10% H2O-air atmospheres. A record of over 230 h is achieved in the long-term stability test in the EC mode, doubling the longest test that had been previously reported. Besides good stability, SEFC demonstrates great catalytic activity toward air electrode reactions when compared with traditional La0.6Sr0.4Co0.2Fe0.8O3-δ air electrodes. This research highlights the potential of stable and efficient P-RSOCs as an important part in a sustainable new energy power system.

A first-principles study on divergent reactions of using a Sr3Fe2O7 cathode in both oxygen ion conducting and proton conducting solid oxide fuel cells.

Exploring mechanisms for sluggish cathode reactions is of great importance for solid oxide fuel cells (SOFCs), which will benefit the development of suitable cathode materials and then accelerate cathode reaction rates. Moreover, possible reaction mechanisms for one cathode should be different when operating in oxygen ion conducting SOFCs (O-SOFC) and in proton conducting SOFCs (P-SOFCs), and therefore, they lead to different reaction rates. In this work, a Ruddlesden-Popper (R-P) oxide, Sr3Fe2O7 (SFO), was selected as a promising cathode for both O-SOFCs and P-SOFCs. Using the first-principles approach, a microscopic understanding of the O2 reactions over this cathode surface was investigated operating in both cells. Compared with La0.5Sr0.5Co0.25Fe0.75O3 (LSCF), the low formation energies of oxygen vacancies and low migration energy barriers for oxygen ions in SFO make oxygen conduction more preferable which is essential for cathode reactions in O-SOFCs. Nevertheless, a large energy barrier (2.28 eV) is predicted for oxygen dissociation reaction over the SFO (001) surface, while there is a zero barrier over the LSCF (001) surface. This result clearly indicates that SFO shows a weaker activity toward the oxygen reduction, which may be due to the low surface energies and the specific R-P structure. Interestingly, in P-SOFCs, the presence of protons on the SFO (001) surface can largely depress the energy barriers to around 1.46-1.58 eV. Moreover, surface protons benefit the oxygen adsorption and dissociation over the SFO (001) surface. This result together with the extremely low formation energies and migration energy barriers for protons seem to suggest that SFO could work more effectively in P-SOFCs than in O-SOFCs. It's also suggested that too many protons at the SFO surface will lead to high energy barriers for the water formation process, and thus that over-ranging steam concentrations in the testing atmosphere may have a negative effect on cell performances. Our study firstly and clearly presents the different energy barriers for one cathode performing in both O- and P-SOFCs according to their different working mechanisms. The results will be helpful to find the constraints for using cathodes toward oxygen reduction reactions, and to develop effective oxide cathode materials for SOFCs.

Significance of B10 cell in patients with thymoma complicated with myasthenia gravis.

A subset of regulatory B cells in humans has been identified as B10 cell which has the function of secreting interleukin-10. We evaluated the significance of B10 cell in patients with thymoma complicated with myasthenia gravis. In this study, 156 patients diagnosed with thymoma were enrolled, FCM was used to detected the percentage of Breg/CD19+B cells and CD19+B cells/PBMC, ELISA to evaluate the serum concentration of the relevant immunological markers; purified CD19+B cells in tissues by MACS; gene and protein expressions of CD19 and IL-10 by Real-time PCR and Western-Blot; double immunofluorescence staining to detect the distribution of CD19 and IL-10 in thymus tissues. Thymoma patients without MG mainly display the types A and AB of thymoma, whereas the thymoma patients with MG mainly display type B (B1, B2 and B3) thymoma; AChR-Ab in Tm + MG group was the highest, with the progress of the disease, the percentage of Breg/CD19+B cells increased and B10/CD19+B cells decreased (p < 0.05); ROC curve showed that B10 had the greatest significance for the clinical directivity of Tm+MG and cut-off point = 0.55%; in accordance with the Con, Tm and Tm+MG group, the content of CD19+IL-10+B10 cells increased gradually (p < 0.05); meanwhile, the gene and protein expression levels of CD19 and IL-10 gradually increased in the same way. It is concluded that with the progress of thymoma, the infiltration of Breg in tumour tissue increases; however, as the severity of MG increases, the function of Breg (B10 cell) in peripheral blood decreases and the cut-off point is 0.55%.

Esmolol reduces apoptosis and inflammation in early sepsis rats with abdominal infection.

BACKGROUND: Esmolol is a highly selective beta 1 receptor blocker with various effects such as slowing heart rate, lowering blood pressure and reducing myocardial oxygen consumption. However, few studies have reported the use of beta blockers in sepsis with multiple organ dysfunctions. This study aimed to investigate the effects of esmolol on reducing apoptosis and inflammation in early sepsis rats with abdominal infection. METHODS: Rats were randomly divided into sham operation group, sepsis group, antibiotic group, Esmolol + antibiotic group with low, median and high dose Esmolol (L group, M group and H group). Values between two or more groups were compared by independent t-tests. RESULTS: In the liver and kidney, we found inflammatory infiltration in sepsis group while pathological aspects reduced in L, M and H groups. Bcl-2 mRNA and protein levels increased while Bax mRNA and protein levels decreased in the liver and kidney of L, M and H groups. Serum IL-6, HMGB-1 and TNF-α levels decreased but IL-10 level increased in L, M and H groups, compared to sepsis group. Compared to sepsis and antibiotic groups, the levels of myocardial enzymes were lower in L, M and H groups. CONCLUSION: The administration of esmolol in early sepsis may reduce inflammation, inhibit apoptosis and protect key organs.