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Yang Song,1,2 Dake Hao,3 Huan Jiang,4 Mingguang Huang,2 Qingjun Du,2 Yi Lin,2 Fei Liu,1 Bin Chen1 1Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Division of Traumatology and Joint, Department of Orthopaedics, Shunde Hospital, Southern Medical University, Foshan, 528308, People’s Republic of China; 3Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA; 4Department of Anesthesiology, Shunde Hospital, Southern Medical University, Foshan, 528308, People’s Republic of ChinaCorrespondence: Bin ChenDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaEmail chb@smu.edu.cnIntroduction: Post-traumatic osteoarthritis (PTOA) is an inflammatory condition that occurs following mechanical joint trauma and that results in joint degeneration. This study sought to evaluate the regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in a murine model of anterior cruciate ligament transection (ACLT)-induced PTOA and in an in vitro model of synoviocyte inflammation induced by LPS treatment with the goal of exploring the role of chitinase 3-like-1 (CHI3L1) in this pathogenic context.Methods: PTOA model mice were intra-articularly injected with Nrf2 overexpression lentiviral vector, and safranin O-fast green staining as well as the Osteoarthritis Research Society International (OARSI) Scoring System were used to evaluate the severity of cartilage damage. Protein expression in the synovial tissue was evaluated by Western blotting, immunohistochemical staining, and ELISA. Additionally, murine synoviocytes were infected with Nrf2 overexpression lentivirus and stimulated with LPS. The levels of inflammatory cytokines were detected by ELISA. ROS levels were measured using dihydroethidium (DHE) dye.Results: We determined that the overexpression of Nrf2 was sufficient to reduce cartilage degradation in the context of PTOA in vivo, and we observed a significant decrease in the expression of matrix metalloproteinase 13 (MMP13) in the articular cartilage of samples from mice overexpressing Nrf2 relative to control mice. Synovial CHI3L1 expression and serum TNF-α, IL-1β, and IL-6 levels were reduced in animals overexpressing this transcription factor relative to PTOA model controls. Consistent with these findings, murine synoviocytes treated with LPS exhibited dose-dependent increases in ROS, TNF-α, IL-1β, IL-6, Nrf2, and CHI3L1 levels, whereas Nrf2 overexpression was sufficient to suppress these increases.Conclusion: Our data indicated that Nrf2 negatively regulates CHI3L1, suggesting that this signaling axis may regulate PTOA progression and may thus be a viable therapeutic target in individuals affected by this condition.Keywords: post-traumatic osteoarthritis, synovium, Nrf2, CHI3L1, oxidative stress, inflammation

The genus Bidens (Asteraceae) encompasses over 240 different species. One of them is Bidens pilosa L. that is an easy‐to‐grow perennial, and broadly distributed in tropical and subtropical regions of the world. This plant has been regarded as an edible plant by the Food and Agriculture Organization of the United Nations since 1975, and has been traditionally used as a food and medicine in America, Africa, and Asia. B. pilosa has been claimed to possess active compounds with more than 40 distinct bioactivities. Although considerable progress has been made in studying the phytochemistry and biology of B. pilosa and its compounds over recent years, a critical review of its dietary functions for metabolic syndrome is unavailable. The present review summarizes the nutrition, benefits, phytochemistry, and safety of B. pilosa with respect to metabolic syndrome. As well as highlighting studies of the use of B. pilosa for metabolic syndrome, scientific evidence regarding the antimetabolic action, mechanism, and application of this species and its active phytochemicals are discussed. This review consolidates information for further study into the medicinal benefits of the compounds in this plant.

Loss of β‐cell number and function is a hallmark of diabetes. β‐cell preservation is emerging as a promising strategy to treat and reverse diabetes. Here, we first found that Pdia4 was primarily expressed in β‐cells. This expression was up‐regulated in β‐cells and blood of mice in response to excess nutrients. Ablation of Pdia4 alleviated diabetes as shown by reduced islet destruction, blood glucose and HbA1c, reactive oxygen species (ROS), and increased insulin secretion in diabetic mice. Strikingly, this ablation alone or in combination with food reduction could fully reverse diabetes. Conversely, overexpression of Pdia4 had the opposite pathophysiological outcomes in the mice. In addition, Pdia4 positively regulated β‐cell death, dysfunction, and ROS production. Mechanistic studies demonstrated that Pdia4 increased ROS content in β‐cells via its action on the pathway of Ndufs3 and p22phox. Finally, we found that 2‐β‐D‐glucopyranosyloxy1‐hydroxytrideca 5,7,9,11‐tetrayne (GHTT), a Pdia4 inhibitor, suppressed diabetic development in diabetic mice. These findings characterize Pdia4 as a crucial regulator of β‐cell pathogenesis and diabetes, suggesting Pdia4 is a novel therapeutic and diagnostic target of diabetes., Pancreatic β‐cell failure is associated with diabetes. Pdia4, a protein disulfide isomerase, is identified as a crucial regulator of β‐cell pathogenesis and diabetes.

This study aims to investigate the curative effects and mechanism of radiofrequency ablation nucleoplasty in the treatment of cervical vertigo.A total of 27 patients diagnosed with cervical vertigo from January 2012 to October 2014 received treatment of radiofrequency ablation nucleoplasty. The narrow-side vertebral artery diameters were examined by using Philips 1.5-T body dual-gradient MRI system. The haemodynamic parameters were detected by using transcranial Doppler sonography. Both of the vertebral artery diameters and haemodynamic parameters were recorded and compared before and after treatment. The curative effects in early post-operative application were evaluated according to the Nagashima standards.Radiofrequency ablation nucleoplasty was performed in a total of 59 cervical discs in 27 patients. The average operation time was 42.7 min, and the symptoms of 92.6% patients were alleviated after radiofrequency ablation nucleoplasty post-operation application. There was no significant difference in the narrow-side vertebral artery diameters before and after treatment in both Group A (p = 0.12) and Group B (p = 0.48); however, the blood flow velocity was significantly higher than that before treatment in both Group A (p = 0.01) and Group B (p = 0.03), respectively.Radiofrequency ablation nucleoplasty improves the blood flow in the narrow-side vertebral artery and illustrates the therapeutic effect on cervical vertigo in patients who have no direct compression of the vertebral artery. Advances in knowledge: Radiofrequency intradiscal nucleoplasty can be used as a minimally invasive procedure for treating cervical vertigo.

For those products that are heavily competitive in the marketplace, demand volatility and unpredictability have been growing. This has resulted in a sizeable deviation in demand forecasts when using the traditional forecasting methods. Accordingly, this study aims to develop a real option approach-based forecasting model for predicting demand during the upcoming planning horizon for products with high random volatility on demand. The real option approach can effectively deal with the long-term trends and random variation involved in a given demand stochastic diffusion process. Additionally, this study proposes taking Monte Carlo simulation as a numerical method to solve the demand-forecasting model. Monte Carlo simulation not only can accurately approximate almost any type of stochastic processes, but also can competently handle the path-dependant relationship existing between successive demands. Subsequently, these demand forecasts are used to determine the provisioned smoothing capacity during the upcom...

With demand variability and unpredictability, decreasing product life cycles, globalisation and increasing competition, rush orders are increasingly being received at job shops. However, these rush orders can be difficult to fulfil owing to a lack of capacity during boom and heavy workload periods. In this situation, a feasible solution is capacity exchange, through which capacity is transacted and exchanged with other customers for whom the manufacturer has already reserved capacity. Accordingly, this study develops a customer-driven capacity exchange mechanism for solving the foregoing problem of temporary capacity shortage caused by the receipt of rush orders in a job shop. Notably, this innovative concept and mechanism can be expected to concurrently benefit capacity holders, capacity demanders and manufacturers. Additionally, this study presents a comprehensive design scheme, working scenario, and possible implementation for a capacity exchange mechanism.

The complicated nature of the semiconductor manufacturing process requires high precision and thousands of spare parts. Due to the characteristics of high cost, as well as dynamic demand rate for spare parts of semiconductor equipment, spare parts inventory management is always an important issue for the equipment supplier. In this paper, we focus on the case of spare parts with high cost and low usage. Using varying lead times and machine life cycles, a simple model to evaluate the relationship between inventory level and service level is developed and a moving sum method is used to estimate the parameters of the model while only a small set of demand data is available. Then we take Applied Materials Taiwan (AMT), a major semiconductor equipment manufacturer in Taiwan, as an example to demonstrate the estimation of parameters of lead time distribution and parts demand rate and the implementation of the inventory model.

This study investigates the buffer allocation strategy of a flow-shop-type production system that possesses a given total amount of buffers and finite buffer capacity for each workstation as well as general interarrival and service times in order to optimize such system performances as minimizing work-in-process, cycle time and blocking probability, maximizing throughput, or their combinations. In theory, the buffer allocation problem is in itself a difficult NP-hard combinatorial optimization problem, it is made even more difficult by the fact that the objective function is not obtainable in closed form for interrelating the integer decision variables (i.e., buffer sizes) and the performance measures of the system. Therefore, the purpose of this paper is to present an effective design methodology for buffer allocation in the production system. Our design methodology uses a dynamic programming process along with the embedded approximate analytic procedure for computing system performance measures under a certain allocation strategy. Numerical experiments show that our design methodology can quickly and quite precisely seek out the optimal or sub-optimal allocation strategy for most production system patterns.

This study extends previous results for batch-service workstations to batch-service/batch-lot workstations with multiple process recipes, e.g., diffusion operations in semiconductor manufacturing. The model considered herein explicitly considers the existence of a manufacturing operation associated with multiple process recipes in the semiconductor factory. Consequently, the revised balance equations are submitted and an improved approximation is presented for this case. Based on a comparison with simulation results, this new approximation is shown to be superior to the previously developed analytical approaches. This new approximation is especially strong in cases where the number of process recipes grows, system traffic intensity is moderate, and arrival rate of each recipe is nearly the same.

To investigate the therapeutic effects of different skin flaps for repairing severe complex hand injuries with burns and compression.From January 1990 to December 2000, 39 patients with severe complex injuries due to burns and compression in the hand were treated with different skin flaps, followed by early-stage postoperative comprehensive rehabilitation therapy.All the patients were followed up for 6 to 12 months, and significant differences were observed in the appearance and function of the repaired hands with different skin flaps.The medial skin flap taken from the lower leg and the reverse-flow island flap from the anterior aspect of the forearm, when combined with early postoperative rehabilitation treatment, can achieve good recovery of function and appearance of the injured hand.

To evaluate the clinical effect of total hip joint replacement and hemiarthroplasty in treatment of fracture of femoral neck in old patients.One hundred and ten cases with femoral neck fracture in the aged, 70 to 106 years old, from Aug 1990 to Aug 1999 were reviewed, 96 cases were followed up, among which 52 cases received total hip joints replacement and the other 44 cases received hemiarthroplasty. All of the 96 cases were followed up for 15 to 112 months, averaged 51 months, and were evaluated in operation procedures, post-operative recovery and joint function according to Harris Scoring.The operation time of total hip joints replacement was 20 minutes longer, bleeding volume was 120 ml larger, and post-operative drainage was 140 ml more, in average, than those in hemiarthroplasty. There was no obvious difference between the two types of operation in bed-resting time, length of stay and hospitalizing costs. According to Harris Scoring, there were 38 cases of excellent in hemiarthroplasty (86.4%) and 48 cases of excellent in total hip joints replacement (92.3%).Both of the artificial joint replacements are reasonable choices for treatment of fracture of femoral neck in old patients, but total hip joints replacement is recommendable for those comparatively younger patients with good systematic status, and hemiarthroplasty is a good option for those elderly with some systematic diseases.