Hybrid shrinking projection method for a generalized equilibrium problem, a maximal monotone operator and a countable family of relatively nonexpansive mappings

AbstractThe purpose of this paper is to introduce and consider a hybrid shrinking projection method for finding a common element of the set EP of solutions of a generalized equilibrium problem, the set ⋂n=0∞F(Sn) of common fixed points of a countable family of relatively nonexpansive mappings {Sn}n=0∞ and the set T−10 of zeros of a maximal monotone operator T in a uniformly smooth and uniformly convex Banach space. It is proven that under appropriate conditions, the sequence generated by the hybrid shrinking projection method, converges strongly to some point in EP∩T−10∩(⋂n=0∞F(Sn)). This new result represents the improvement, complement and development of the previously known ones in the literature

Enhancing crispr-mediated CHO cell antibody productivity through concentrated fed- batch or continuous perfusion

Integrated continuous bioprocessing technology has high productivity and cost saving benefit, which combines the upstream (Cell culture) and downstream (Purification) processing. The continuous bioprocessing based biopharmaceutical manufacturing is more profitable than traditional batch/fed-batch processing in increasing quality and quantity. The goal of this study focuses on the upstream continuous process development with crispr-mediated targeted gene integration CHO cell line producing monoclonal antibody. In the upstream processing, we developed concentrated fed-batch culture (CFB) and high density perfusion culture in 2-5 L bioreactor with a cell retention device (alternating tangential flow, ATF). With our concentrated fed-batch culture system, the VCD achieved 8.4x107 cells/m in 11days operation with 1VVD producing antibody 3.3-fold that of fed-batch culture system; in the high density perfusion culture system, the VCD achieved 5x107 cells/ml in 28 days operation with 1 VVD producing antibody greater than 1g/L/day with on the Day10 and keep the cell density, viability and productivity more than 1 month

Bioprocess intelligent for the improvements and prediction on fed-batch cell culture in bioreactor

With advances in biotechnology, the antibody productivity is not the only issue in biopharmaceutical manufacturing; moreover, how to control the quality and quantity of antibody production in bioprocess has become prominent. In typical fed-batch cell culture, it is not easy to control the dynamic cultivation and feeding conditions. The study is to present an intelligent bioprocess make use of design of experiments (DOE) and multivariate data analysis (MVDA). In the culture medium optimization, we performed the medium screening with the DOE method in shake spin tubes and shake flasks. DOE provides a cost-effective methodology for medium development and optimization, and furthermore we utilized multivariate data analysis methodology to build up the fed-batch intelligence bioprocess in 5 L bioreactor. We analyzed mass data transferred from 5 L bioreactor process and established the fed-batch culture model with SIMCA software. Combination of the batch process and big data sets, we can be easy to do batch-to-batch comparison, cell culture profile prediction, and key parameter finding to improve the process performance with more steady product quality and less error. In this fed-batch culture model, we achieved more than 5 g/L cell productivity consistently and predictably in 5 L bioreactor cultivation with CRISPR-mediated targeted gene site-specific integration CHO cell line

Association of Chinese Herbal Medicines Use with Development of Chronic Obstructive Pulmonary Disease Among Patients with Rheumatoid Arthritis: A Population-Based Cohort Study

Purpose: Rheumatoid arthritis (RA) patients appear to report a higher risk of chronic obstructive pulmonary disease (COPD). While Chinese herbal medicine (CHMs) is proven to lower COPD risk, the scientific evidence regarding its effect in relation to COPD onset among them is limited. This longitudinal cohort study aimed to determine the relationship between CHMs use and the COPD risk in RA patients. Methods: Using the nationwide claim data, 8349 patients newly diagnosed with RA and simultaneously free of COPD between 1998 and 2010 were eligible for enrollment. From this sample, we enrolled 3360 CHMs users and 3360 non-CHMs users, randomly selected using propensity scores matching from the remaining cases. They were followed until the end of 2012 to record COPD incidence. The hazard ratio (HR) of COPD with regard to CHMs use was estimated by the Cox proportional hazards regression model. Results: In the follow-up period, 136 CHMs users and 202 non-CHMs users developed COPD, representing incidence rates of 5.16 and 7.66, respectively, per 1000 person-years. CHMs use was associated with a 32% lower subsequent risk of COPD (adjusted HR: 0.68, 95% Confidence Interval: 0.54–0.84). Eight commonly prescribed CHMs were discovered to be associated with lower COPD risk: Yan Hu Suo, Sānɡ Zhī, Dang Shen, Huang Qin, Jia-Wei-Xiao-Yao-San, Shu-Jing-Huo-Xue-Tang, Du-Huo-Ji-Sheng-Tang and Ge-Gen-Tang. Conclusion: A significant association of CHMs use with a lower risk of COPD onset in RA patients was found, suggesting that CHMs could be integrated into conventional therapy to reduce COPD risk

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC. METHODS: Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionation of urine protein prior to two-dimensional gel electrophoresis. RESULTS: Fifty five differential proteins have been determined by comparing with the 2-DE maps of the urine of UTUC patients and those of healthy people. Western blotting analysis and immunohistochemistry of tumor tissues and normal tissues from patients with UTUC were carried out to further verify five possible UTUC biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2, annexin A3 and haptoglobin. The data of western blot and immunohistochemical analysis are consistent with the 2-DE data. Combined the experimental data in the urine and in tumor tissues collected from patients with UTUC, the crucial over-expressed proteins are calreticulin, annexin A2, and annexin A3. CONCLUSIONS: Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers with potential value for UTUC diagnosis

Decreased Risk of Osteoporosis Incident in Subjects Receiving Chinese Herbal Medicine for Sjögren Syndrome Treatment: A Retrospective Cohort Study with a Nested Case-Control Analysis

Sjögren syndrome (SS) is a long-lasting inflammatory autoimmune disease that may cause diverse manifestations, particularly osteoporosis. Though usage of Chinese herbal medicine (CHM) can safely manage autoimmune disease and treatment-related symptoms, the relation between CHM use and osteoporosis risk in SS persons is not yet recognized. With that in mind, this population-level nested case-control study aimed to compare the risk of osteoporosis with and without CHM use. Potential subjects aged 20–70 years, diagnosed with SS between 2001 and 2010, were retrieved from a national health claims database. Those diagnosed with osteoporosis after SS were identified and randomly matched to those without osteoporosis. We capitalize on the conditional logistic regression to estimate osteoporosis risk following CHM use. A total of 1240 osteoporosis cases were detected and randomly matched to 1240 controls at a ratio of 1:1. Those receiving conventional care plus CHM had a substantially lower chance of osteoporosis than those without CHM. Prolonged use of CHM, especially for one year or more, markedly dwindled sequent osteoporosis risk by 71%. Integrating CHM into standard care may favor the improvement of bone function, but further well-designed randomized controlled trials to investigate the possible mechanism are needed

Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyl)lysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE) than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox) capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T) and polymorphonuclear neutrophils (PMN) of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px) and γ-glutamyl-transpeptidase (GGT), was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients

Routinely transradial arterial approach for extra-cranial carotid stenting

BackgroundThe purpose of this study is to report a single center experience with its safety and feasibility of transradial arterial (TRA) approach in extra-cranial carotid artery (ECCA) stenting.Methods and results74 patients were consecutively enrolled in this study. A retrograde-engagement technique, involving looping 6-F Kimny guiding catheter, was utilized for ECCA angiographic study. For ECCA stenting, the 6-F Kimny guiding catheter was replaced with a 7-F Kimny guiding catheter and the procedure was performed as the follows. First, a 0.035-in. Teflon wire was carefully advanced into the common CA. Second, a PercuSurge GuardWire was inserted into the external CA, followed by distal balloon inflation for an anchoring support. Third, the 6-F guiding catheter was removed, followed by exchanging a 7-F kimny guiding catheter which was advanced along the 0.035-in. Teflon wire and the PercuSurge GuardWire to proximal part of common CA. Distal protection device was then utilized to protect from distal embolization during the procedure. One procedure failed due to external CA did not provide an anchoring support. Thus, the procedure was successful in 74 (98.7%) patients. No vascular or bleeding complication was observed. Minor stroke occurred in 3 (4.0%) patients during the procedure. All of them were completely recovery within 1week.ConclusionsThe TRA approach for ECCA stenting is safe and feasible. This access may offer a last resort for patients with unsuited to femoral arterial access and endarterectomy

Hybrid Algorithms for Solving Variational Inequalities, Variational Inclusions, Mixed Equilibria, and Fixed Point Problems

We present a hybrid iterative algorithm for finding a common element of the set of solutions of a finite family of generalized mixed equilibrium problems, the set of solutions of a finite family of variational inequalities for inverse strong monotone mappings, the set of fixed points of an infinite family of nonexpansive mappings, and the set of solutions of a variational inclusion in a real Hilbert space. Furthermore, we prove that the proposed hybrid iterative algorithm has strong convergence under some mild conditions imposed on algorithm parameters. Here, our hybrid algorithm is based on Korpelevič’s extragradient method, hybrid steepest-descent method, and viscosity approximation method