Electrochemical Dynamics of a Single Platinum Nanoparticle Collision Event for the Hydrogen Evolution Reaction.

Chronoamperometry was used to study the dynamics of Pt nanoparticle (NP) collision with an inert ultramicroelectrode via electrocatalytic amplification (ECA) in the hydrogen evolution reaction. ECA and dynamic light scattering (DLS) results reveal that the NP colloid remains stable only at low proton concentrations (1.0 mm) under a helium (He) atmosphere, ensuring that the collision events occur at genuinely single NP level. Amperometry of single NP collisions under a He atmosphere shows that each discrete current profile of the collision event evolves from spike to staircase at more negative potentials, while a staircase response is observed at all of the applied potentials under hydrogen-containing atmospheres. The particle size distribution estimated from the diffusion-controlled current in He agrees well with electron microscopy and DLS observations. These results shed light on the interfacial dynamics of the single nanoparticle collision electrochemistry.

Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways.

OBJECTIVE: We investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3). METHODS: Cytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish. RESULTS: Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01). CONCLUSIONS: Docosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy.

Liraglutide reduces the body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients.

AIM: To investigate the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor activator, on body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. METHODS: A total of 328 Chinese overweight and obese type 2 diabetic patients were included in this multi-center, open-labeled and self-controlled clinical study. The patients were subcutaneously injected with liraglutide once daily for 24 weeks as add-on therapy to their previous hypoglycemic treatments. Statistical analyses were performed using SPSS software package version 11.5 for Windows. RESULTS: Liraglutide treatment caused significant reduction of the mean body weight (from 86.61±14.09 to 79.10±13.55 kg) and waist circumference (from 101.81±13.96 to 94.29±14.17 cm), resulting in body weight lose of 5%-10% in 43.67% patients, and body weight loss above 10% in 34.06% patients, who had significant lower plasma creatinine levels. Baseline waist circumference, BMI and HOMA-IR were independently correlated with the body weight loss. Furthermore, liraglutide treatment significantly decreased HbA1c levels (from 8.66%±2.17% to 6.92%±0.95%) with HbA1c<7.0% in 35.37% patients, who had a significantly lower baseline level of HbA1c, but higher baseline levels of C peptide and glucagon. Moreover, liraglutide treatment resulted in greater body weight loss in patients with a long duration of diabetes, and better glycemic control in patients with a short duration of diabetes. CONCLUSION: Liraglutide significantly reduces body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients. Patients with apparent visceral obesity, insulin resistance and a long duration of diabetes may have greater body weight loss; whereas patients with high insulin-secreting ability, hyperglucagonemia, and short-duration diabetes may obtain better glycemic control with liraglutide.

[Correlation between Expression of CD47 Molecule in Patients with Newly Diagnosed Adult Acute Myeloid Leukemia and Clinical Prognosis].

OBJECTIVE: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis. METHODS: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient's initial diagnosis, the relationship between the patient's prognosis and CD47 was evaluated. RESULTS: The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34+, CD38+, CD123+ (P>0.05). The proportion of bone marrow protocells in AML patients was >50%, the ECOG score was >2 points, MLLELL fusion gene and chromosome prognosis stratification were all risk factors affecting the survival of patients (P=0023, 0.036, 0.012, 0.001, respectively). The high expression of bone marrow CD47 in AML patients indicated a high risk of recurrence (P=0.017). CONCLUSION: The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.

[Effect of Herba Scutellariae Barbatae flavonoids in delaying aging of Caenorhabditis elegans and human umbilical vein endothelial cells in vitro].

OBJECTIVE: To explore the effects of Herba Scutellariae Barbatae flavonoids (HF) in delaying aging of Caenorhabditis elegans and human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: The effects of 30 or 50 mg/L of HF on nematode life span, reproductive capacity, oxidative stress, and antioxidant enzyme activity of C. elegans were assessed, and the effects of HF on the expressions of the genes encoding antioxidant enzymes and the aging-related genes were analyzed using real-time RT-PCR in both C. elegans and cultured HUVECs. Results Compared with the blank control group, C. elegans with HF treatment showed significantly improved mean and maximum lifespan with a prolonged mean lifespan under acute heat stress at 35 degrees celsius;. HF treatment did not impair the reproductive capacity or cause significant changes in the offspring number of C. elegans. In addition, HF enhanced SOD and CAT activity and up-regulated the expression of daf-16 and sir-2.1 (SIRT1) genes in C. elegans and HUVECs. CONCLUSIONS: HF may delay aging of C. elegans and enhance their resistance to acute heat stress without damaging their reproductive capacity possibly by up-regulating the activity of antioxidant enzymes and expressions of antioxidant genes. HF also may protect endothelial cells against oxidative damage.

High WAVE3 expression correlates with proliferation, migration and invasion in human ovarian cancer.

BACKGROUND: Wiskott-Aldrich syndrome verprolin-homologous (WAVE) 3, a member of the WASP/WAVE family of proteins, plays a critical role in cell motility and acts as an oncogene in some human cancers, but no sufficient information available to illustrate its involvement in ovarian cancer tumorigenesis and progression. METHODS: The expression of WAVE3 in human ovarian cancer and normal tissue was analyzed by immunohistochemistry. WAVE3 gene and protein expression in different human ovarian cancer cell lines was tested by RT-PCR and western blotting. Stable cells of WAVE3-knockdown in SKOV3 cells or transfected high expression in A2780 cells were constructed. The WAVE3 expression and its correlation with MMPs, p38 MAPK and other factors were studied. The relationship between WAVE3 and oncogenicity in vivo was also evaluated by nude mice xenograft model. RESULTS: Immunohistochemistry staining showed the highest WAVE3 expression in ovarian cancer metastases, high in ovarian cancer and weak in normal. In different cell lines, SKOV3 cells showed the highest WAVE3 expression, A2780 cells expressed the lowest. Elevated WAVE3 expression in A2780 cells promoted proliferation and decreased apoptosis, increased the cell number in G2/M phase and promoted migration significantly. Correspondingly, knockdown of WAVE3 in SKOV3 cells showed opposite effects. The WAVE3 expression showed positive correlation with MMPs, NF-κB, COX-2, VEGF and phospho-p38 MAPK, but not p38. The high expression of WAVE3 promoted tumorigenesis in vivo. CONCLUSIONS: Our results suggested that WAVE3 may be pivotal in ovarian cancer cell motility, invasion and oncogenesis, which might be related with MMPs production and p38 MAPK pathway.

Association of Interleukin-23 Receptor Gene Single Nucleotide Polymorphisms with Ankylosing Spondylitis.

OBJECTIVE: It has been shown previously that the IL-23 receptor (IL-23R) variants are associated with ankylosing spondylitis (AS). It is unknown whether IL-23R is associated with AS in the Chinese population. The present study was performed to examine the association of IL-23R gene polymorphisms with susceptibility to AS in the Chinese population. METHODS: A total of 157 Chinese Han patients with AS and 150 ethnically matched healthy controls were enrolled. All patients were diagnosed with AS according to the modified New York criteria. 8 single nucleotide polymorphisms (SNPs) of the IL-23R gene cluster were genotyped. RESULTS: None of the 8 IL-23R SNPs were found to be associated with AS in the Chinese population. CONCLUSION: The association of IL-23R and AS that is seen in Caucasian patients with AS is not present in Chinese patients with AS.

Comparative Assessment of Different Health Utility Measures in Systemic Lupus Erythematosus.

In a time of increasing economic constraints, it is crucial that health systems optimize their resource use to ensure that they generate the maximum possible health gain. Therefore, it is necessary for health interventions to be evaluated and compared across therapeutic boundaries. Undertaking such an evaluation a generic utility-based measure is required. But it remains uncertain whether the utility values obtained by direct or indirect methods are comparable and which approach is the most appropriate in Systemic Lupus Erythematosus (SLE) population. In the study, we compared the utility values obtained by an indirect method (EQ-5D) with direct utility instruments, the standard gamble (SG) and visual analog scale (VAS), in SLE patients. The correlations between VAS, EQ-5D and LupusQoL were significant; relative good intraclass correlations or kappa coefficients indicated the reliability of these instruments. A model incorporating the SLEDAI scores and LupusQoL domains of emotional health and pain was a good predictor of VAS. SLEDAI score was a good predictor in the SG regression model. These findings suggested that the VAS and EQ-5D might be valid and reliable measures to assess health related quality of life in SLE patients and represent promising outcome measures for future research in this population.

Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS.

Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA) and graphitized carbon blacks (GCB), the contents of signal compounds salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate were determined by GC-MS. The results showed that the level of salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate increased remarkably in U. pumila once infected by T. akinire Sasaki, but the maximums of these four compounds occurred at different times. Salicylic acid level reached the highest at the early stage, and jasmonic acid level went to the maximum in the middle stage; by contrast, change of content of methyl salicylate and methyl jasmonate was the quite opposite.

Construct and criterion validity of the Euro Qol-5D in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the construct and criterion validity of the Euro Qol-5D (EQ-5D), which allows quality-adjusted life-years to be calculated, in patients with systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients who had been followed at the Renji Hospital, School of Medicine, Shanghai Jiao Tong University were recruited. Cross-sectional correlations of the EQ-5D with equivalent domains in disease-specific health-related quality of life (HRQoL), LupusQol, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) measures, the Systemic Lupus International Collaborating Clinics Damage Index (SDI), and patient characteristics were tested. Discriminant validity to assess the ability to distinguish between patients of different disease severity was assessed. There also were evaluations of ceiling and floor effects. RESULTS: 240 patients were recruited in total. The EQ-5D correlated moderately to strongly with all domains of the LupusQoL (r: 0.44-0.7) apart from intimate relationships (r = 0.25) and body image (r = 0.18). There was moderate negative correlation between EQ-5D and clinical assessment of disease, SLEDAI (r = -0.589) and SDI (r = -0.509). When compared with equivalent domains on LupusQoL, there was good construct validity in EQ-5D (r: 0.631-0.812). EQ-5D could also discriminate patients with varied disease severity (according SLEDAI and SDI). There was no floor effect in EQ-5D but the ceiling effect remains strong (34%). CONCLUSION: Our results provide sufficient evidence that the EQ-5D displays construct and criterion validity for use in SLE patients. Disease-specific measures of HRQoL used alongside may be a better choice.

Multi-dimensional health assessment questionnaire in China: reliability, validity and clinical value in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the psychometric properties and clinical utility of Chinese Multidimensional Health Assessment Questionnaire (MDHAQ-C) in patients with rheumatoid arthritis (RA) in China. METHODS: 162 RA patients were recruited in the evaluation process. The reliability of the questionnaire was tested by internal consistency and item analysis. Convergent validity was assessed by correlations of MDHAQ-C with Health Assessment Questionnaire (HAQ), the 36-item Short-Form Health Survey (SF-36) and the Hospital anxiety and depression scales (HAD). Discriminant validity was tested in groups of patients with varied disease activities and functional classes. To evaluate the clinical values, correlations were calculated between MDHAQ-C and indices of clinical relevance and disease activity. Agreement with the Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI) was estimated. RESULTS: The Cronbach's alpha was 0.944 in the Function scale (FN) and 0.768 in the scale of psychological status (PS). The item analysis indicated all the items of FN and PS are correlated at an acceptable level. MDHAQ-C correlated with the questionnaires significantly in most scales and scores of scales differed significantly in groups of different disease activity and functional status. MDHAQ-C has moderate to high correlation with most clinical indices and high correlation with a spearman coefficient of 0.701 for DAS 28 and 0.843 for CDAI. The overall agreement of categories was satisfying. CONCLUSION: MDHAQ-C is a reliable, valid instrument for functional measurement and a feasible, informative quantitative index for busy clinical settings in Chinese RA patients.

Validity of LupusQoL-China for the assessment of health related quality of life in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To adapt and assess the validity and reliability of LupusQoL for use in Chinese patients with systemic lupus erythematosus (SLE). METHODS: Debriefing interviews of subjects with SLE guided the language modifications of the tool. The process of adaptation proceeded according to the guideline and pre-testing results of LupusQoL-China. 220 SLE patients completed LupusQoL-China and a generic preference-based measurement of health EuroQoL scale (EQ-5D), and 20 patients repeated them after 2 weeks. Internal consistency (ICR) and test-retest (TRT) reliability, convergent and discriminant validity were examined. Factor analysis and Rasch analysis were performed. RESULTS: The mean (SD) age of the 208 subjects with SLE was 33.93 (± 9.19) years. ICR and TRT of the eight domains ranged from 0.811 to 0.965 and 0.836 to 0.974, respectively. The LupusQoL-China domains demonstrated substantial evidence of construct validity when compared with equivalent domains on the EQ-5D (physical health and usual activities r = -0.63, pain and pain/discomfort r = -0.778, emotional health and anxiety/depression r = -0.761, planning and usual activities r = -0.560). Most LupusQoL-China domains could discriminate patients with varied disease activities and end-organ damage (according to SELENA-SLEDAI and SLICC-DI). The principal component analysis revealed six factors, and confirmatory factor analysis result of which is similar to eight factors model. CONCLUSIONS: These results provide evidence that the LupusQoL-China is valid as a disease-specific HRQoL assessment tool for Chinese patients with SLE.

Expression, localization and clinical application of exogenous Smith proteins D1 in gene transfected HEp-2 cells.

AIM: To establish an improved substrate for an indirect immunofluorescence test (IIF) to detect anti-Sm antibody. METHODS: Full-length Smith protein D1(Sm-D1) complementary DNA was obtained from human larynx carcinoma cell line HEp-2 by reverse transcription - polymerase chain reaction (RT-PCR) and cloned into the mammalian expression vector pEGFP-C1. The recombinant plasmid pEGFP-Sm-D1 was transfected into HEp-2 cells. The expression, localization and antigenicity of fusion proteins of green fluorescent protein (GFP) in transfected cells were confirmed by means of immunoblotting (IBT), confocal fluorescence microscopy and IIF analysis. Transfected HEp-2 cells were analyzed with reference serum and compared with untransfected HEp-2 cells by IIF. RESULTS: Stable expression of the Sm-D1-GFP was maintained for more than ten generations. This Sm-D1-GFP showed the antigenicity of Sm-D1 with a characteristic phenotype in IIF.Six of 12 serum specimens from systemic lupus erythematosus contained both 29/28 and 13.5 kDa proteins and showed characteristic immunofluorescent patterns. The same phenomenon appeared in 3/6 serum samples which contained 29/28 kDa proteins only. Sera from 10 healthy donors did not react with HEp-Sm-D1 or HEp-2 at 1:80 attenuant degrees. No alteration in expression, localization and morphology was observed when HEp-Sm-D1 or HEp-2 interacted with the reference sera which could react with Ro/SSA, La/SSB, ß2GP1, centromere, histone, and Scl-70 antibodies in routine IIF tests. CONCLUSION: As a new kind of substrate of IIF, HEp-Sm-D1 can be used to detect anti-Sm antibodies. Transfected HEp-2 cells keep the immunofluorescent property of HEp-2 cells in immunofluorescence anti-nuclear antibody (IFANA) test and could potentially be used as substrate for routine IFANA detection.

Cost effectiveness of different treatment strategies in the treatment of patients with moderate to severe rheumatoid arthritis in china.

BACKGROUND: To analyse the cost-effectiveness of traditional disease-modifying anti-rheumatic drugs (tDMARDs) compared to biological therapies from the perspective of Chinese society. METHODOLOGY/PRINCIPAL FINDINGS: A mathematical model was developed by incorporating the clinical trial data and Chinese unit costs and treatment sequences from a lifetime perspective. Hypothetical cohorts with moderate to severe RA were simulated. The primary outcome measure-quality-adjusted life years (QALYs)-was derived from disease severity (HAQ scores). Primary analysis included drug costs, monitoring costs, and other costs. Probabilistic and one-way sensitivity analyses were performed. Treatment sequences that included TNF antagonists and rituximab produced a greater number of QALYs than tDMARDs alone or TNF antagonists plus DMARDs. In comparison with tDMARDs, the incremental cost-effectiveness ratios (ICERs) for etanercept, infliximab, and adalimumab without rituximab were $77,357.7, $26,562.4 and $57,838.4 per QALY and $66,422.9, $28,780.6 and $50,937.6 per QALY, for etanercept, infliximab, and adalimumab with rituximab. No biotherapy was cost-effective under the willingness to pay threshold when the threshold was 3 times the per capita GDP of China. When 3 times the per capita GDP of Shanghai used as the threshold, infliximab and rituximab could yield nearly 90% cost-effective simulations in probabilistic sensitivity analysis. CONCLUSIONS/SIGNIFICANCE: tDMARD was the most cost-effective option in the Chinese healthcare setting. In some relatively developed regions in China, infliximab and rituximab may be a favorable cost-effective alternative for moderate to severe RA.

Characteristics of an scFv antibody fragment that binds to immunoglobulin G of Graves' disease patients and inhibits autoantibody-mediated thyroid-stimulating activity.

Thyroid-stimulating antibodies (TSAbs) are responsible for hyperthyroid Graves' disease (GD). Although two peptides that bind to GD immunoglobulin G (IgG), and some monoclonal antibodies to the TSH receptor (TSH-R), have been reported to inhibit stimulation of cAMP production by patient serum TSAb, our work is the first to use phage-display technology to produce a mouse single-chain Fv antibody fragment (scFv) that binds to GD IgG and acts as a powerful TSAb (and TSH) antagonist. The specificity characteristics and relative affinity (2.8 mol/L) of T17 were identified by competitive inhibition ELISA and thiocyanate elution. The purified T17 scFv was then tested for its effect on stimulation of cAMP production by Graves' patients' sera in TSH receptor-transfected Chinese hamster ovary (CHO) cells. T17 was an effective antagonist of TSAb activity in 13 of 16 patients with GD. In addition, (125)I-TSH binding to TSH-R was also inhibited by T17 (57% inhibition at 1 mg/mL). This new scFv suggests in vitro applications such as purification of TSAb or diagnosis of GD. In addition, it may have in vivo usefulness such as treatment of TSH-R mediated ophthalmic symptoms of Graves' disease.