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Aim Materials and Methods Results Conclusion Insulin icodec is a first once‐weekly administration basal insulin analogue for type 2 diabetes. This study aimed to investigate the price range of icodec for type 2 diabetes in the Chinese market, taking insulin degludec as reference.Long‐term health outcomes and costs for icodec and degludec were simulated using the United Kingdom Prospective Diabetes Study Outcomes Model (version 2.1) over 40 years from the Chinese healthcare provider's perspective. The efficacy and safety data were obtained from the ONWARDS 2 trial (Switching to once‐weekly insulin icodec versus once‐daily insulin degludec in individuals with basal insulin‐treated type 2 diabetes (ONWARDS 2): a phase 3a, randomised, open label, multicentre, treat‐to‐target trial). Cost–utility analysis and a binary search were used to investigate the price range of icodec. Sensitivity analyses were performed to verify the robustness of the base‐case analysis results.After a 40‐year simulation, the quality‐adjusted life years (QALY) of icodec and degludec were 10.32 and 10.28 years, respectively. At the initial assumption of the same annual costs of icodec and degludec of $455.40, icodec was the dominant therapy compared with degludec, with higher QALYs and lower total cost. After the binary search, we observed that the annual cost range of icodec was $625.17–$855.25. This cost range was finally adjusted to be $597.66–$736.34 using one‐way sensitivity analysis and confirmed using probabilistic sensitivity analysis and scenario analysis. The scenario analysis revealed that the annual cost range of icodec could be $506.70–$736.34 if the price of degludec decreased by 20% in the future.Insulin icodec appears to be more cost effective than degludec if the annual cost of icodec ranges from $597.66 to $736.34 for patients with type 2 diabetes in China. [ABSTRACT FROM AUTHOR]

Aim: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. Methods: The patient cohort and clinical efficacy data were derived from the SURPASS‐2 trial. Cost‐utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. Results: After lifetime simulation, the quality‐adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost‐effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61‐$1846.23, $1738.40‐$2140.95 and $1800.30‐$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68‐$1757.57, $1573.00‐$1967.16 and $1576.54‐$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. Conclusions: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00‐$1967.16 and $1576.54‐$2133.96, respectively, for patients with type 2 diabetes in China. [ABSTRACT FROM AUTHOR]

This article discusses the effectiveness and safety of once-weekly subcutaneous semaglutide compared to other glucose-lowering agents in real-world patients with type 2 diabetes. The study included 502 participants treated with semaglutide and 511 participants treated with other agents. The results showed that semaglutide was associated with significant improvements in glycemic control, weight loss, and cardiovascular risk factors. Additionally, a higher proportion of patients in the semaglutide group achieved the target HbA1c level compared to the non-GLP-1RA group. The study concludes that semaglutide can be beneficial for the management of type 2 diabetes in routine clinical practice. [Extracted from the article]

Background: Stanford type B aortic dissection (TB‐AD) is a life‐threatening vascular condition with high rates of morbidity and mortality. Currently, thoracic endovascular aortic repair (TEVAR) is widely performed to treat TB‐AD, and some studies have analyzed the influence of stents on hemodynamics using computational fluid dynamics (CFD) models. However, the accuracy of TB‐AD simulation models are not satisfactory, they are often constructed as a regular ideal model. Furthermore, it is unclear which tear should be closed for the best treatment when there are multi entry tears. Purpose: The aims of this paper were to provide an assessment method for the selection of the surgical closure location for type B aortic dissection. Five 3D models of multiple entry tears in type B aortic dissection were produced using real patient computed tomography (CT) images to perform hemodynamic analyses of flow velocity streamlines, wall pressure, and wall shear stress. Methods: A Boolean operation was adopted to establish 3D models with multiple entry tears in type B aortic dissection based on patient‐specific CT images. The Mimics and Ansys plug‐in The Integrated Computer Engineering and Manufacturing code for Computational Fluid Dynamics (ICEM CFD) software were applied to mesh the 3D models. The flow velocity streamlines, wall pressures, and wall shear stresses were then analyzed in the finite element analysis software Fluent. Five 3D models were produced to compare the hemodynamic characteristics of different entry tear numbers, as well as the changes of different closure positions before and after closure. Results: The false lumen of the model with two entry tears had a higher wall pressure than that of model with multiple entry tears, which may tend to squeeze the true lumen and expand the false lumen. The load distribution of the vessel in the model with multiple entry tears had a more balanced flow velocity, and its wall pressure and shear stress were lower than that of model with two entry tears. For aortic dissection with two entry tears, the closure of the proximal entry tear was recommended, which helped to isolate and thrombose the false lumen, thereby improving the blood supply function of the true lumen. Because the postoperative vascular flow velocity and mechanical load performance of the vascular wall were still higher than those of normal blood vessels, the postoperative blood vessels remained pathological, and TEVAR did not restore the blood vessels to their original healthy state. Conclusions: Type B aortic dissection with two entry tears tend to squeeze the true lumen and expand the false lumen, resulting in a new entry tear and deterioration into multiple entry type B aortic dissection. The model of the vessel with multiple entry tears had a more balanced distribution in flow velocity and a smaller wall pressure and shear stress than that of the vessel with two entry tears. The closure of the proximal entry tear was considered an ideal solution for type B aortic dissection with two entry tears. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of intracellular water (ICW) evaluated by the bioelectrical Impedance Spectroscopy (BIS) on the risk of incident cognitive impairment (CI) in chronic hemodialysis (HD) patients. Methods: Three thousand three hundred eighty‐five patients were recruited and monitored prospectively for up to 3 years (the median follow‐up time, 2 years) in this observational cohort study. Mini‐Mental State Examination score (MMSE) was used to assess the global cognitive function. ICW was measured by body composition monitor based on BIS. Multiple Cox regression models, stratified analyses, and interactive analyses were conducted. Results: During the follow‐up period, 1256 patients (37.1%) experienced incident CI. The incidence of CI was increased with decreasing quartiles of ICW (27.4%, 32.2%, 38.9%, and 50.1% for the fourth, third, second, and first quartiles, respectively). Decreased ICW was significantly associated with incident CI. The association remained statistically significant even after adjusting for age, sex, education, albumin, C‐reactive protein, residual renal function and various medical histories. The hazard ratios were 1.38 (1.17–1.64) and 1.28 (1.08–1.52) for ICW quartile 1 and quartile 2, respectively (reference, quartile 4). The association stably existed across subgroups, and the residual renal function had an interactive role in the association between ICW and incident CI (p = 0.014). Conclusion: Low baseline ICW was an independent risk factor for CI in chronic HD patients. Our finding highlights the necessity of using BIS to measure body composition when assessing the risk of CI in HD patients. Key points: Cognitive impairment (CI) is a common complication in patients undergoing hemodialysis (HD), causing poor patient prognosis.Body composition is reported to be associated with the risk of CI; however, there is limited evidence about the relationship between body cell waters and CI.In this observational cohort study involving 3385 patients, low baseline intracellular water (ICW) was an independent risk factor for incident CI in chronic HD patients, which provides a basis for monitoring the changes of ICW. [ABSTRACT FROM AUTHOR]

Existing bone tissue engineering strategies aim to achieve minimize surgical trauma, stabilize the injured area, and establish a dynamic osteogenic microenvironment. The cutting‐edge bone glue developed in this study satisfies these criteria. Inspired by the excellent adhesive properties of mussels, herein, a super osteogenic glue (L‐DPZ) that integrates poly(vinyl alcohol), L‐dopa amino acid, and zeolitic imidazolate framework‐8 characterized by catechol–metal coordination is used to successfully adhere to hard tissue with a maximum adhesive strength of 10 MPa, which is much higher than those of commercial and previously reported bone glues. The stable hard tissue adhesion also enables it to adhere strongly to luxated or broken teeth, Bio‐Oss (a typical bone graft material), and splice fragments from comminuted fractures of the rabbit femur. Then, it is testified that the L‐DPZ hydrogels exhibit satisfactory biocompatibility, stable degradability, and osteogenic ability in vitro. Moreover, the ability to anchor Bio‐Oss and sustained osteogenesis of L‐DPZ result in satisfactory healing in calvarial bone defect models in rabbits, as observed by increased bone thickness and the ingrowth of new bone tissue. These results are expected to demonstrate solutions to clinical dilemmas such as comminuted bone fracture fixation, bone defect reconstruction, and teeth dislocation replantation. [ABSTRACT FROM AUTHOR]

Introduction: The main research purpose is to compare the long‐term cost‐effectiveness of semaglutide (SEMA) with that of dulaglutide (DULA) for patients with inadequately controlled type 2 diabetes throughout their lifetime. If necessary, the second aim is to investigate a further price cut for SEMA to provide sound advice for government drug price adjustments. Methods: Cost‐utility analysis was performed by the United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS OM2) from the perspective of health care providers in China. Baseline characteristics and clinical efficacy of SEMA and DULA were sourced from the high‐dose comparison in the SUSTAIN‐7 trial. A binary search was used to identify the scope for further reduction in the price of SEMA. The impact of individual parameters was assessed with sensitivity analyses. Results: Main analysis (SEMA vs. DULA) revealed a mean difference in quality‐adjusted life years (QALYs) of 0.04 QALYs and costs of $1132.29. The incremental cost‐utility ratio was $26 957.44/QALY, showing that SEMA was a better option compared with DULA. In sensitivity analyses, the discount rate made the greatest contribution to the incremental cost‐utility ratio. In the binary search, there was still scope to reduce the SEMA cost further by approximately 6.83% to be cost‐effective, taking DULA as a reference. Conclusion: After its addition to the National Medical Insurance System in China, SEMA is expected to be a cost‐effective choice compared with DULA for patients with type 2 diabetes with inadequately controlled from the cost‐utility analysis. However, there is still scope to reduce the annual cost of SEMA further. [ABSTRACT FROM AUTHOR]

Risk of implant failure increases profoundly in patients with pre‐existing conditions (e.g., diabetes). Current therapies adopt a one‐sided focus on the direct antibacterial properties of biomaterials and osteogenesis stimulation. However, in this study it is demonstrated that a "chain armor" structure (Ce‐TA) that mainly targets the regulation of the local pathological microenvironment, provides a novel solution to scavenge reactive oxygen species (ROS) by simulating superoxide dismutase and catalase and significantly improving osteointegration under diabetic conditions. Ce‐TA based on a metal phenolic network biological functional interface is successfully constructed. Ce‐TA, an ultrathin armor structure, is biocompatible and facile. Through in vitro assays it is demonstrated that Ce‐TA reshapes the diabetic microenvironment into a regenerative one in a microenvironment‐responsive manner, where Ce‐TA regulates hypoxia‐inducible factor 1α (HIF‐1α) activity by reducing the level of mitochondrial ROS, and effectively alleviates mitochondrial dysfunction and reprogrammes macrophages to a pro‐healing state. Furthermore, it is confirmed that Ce‐TA shows excellent therapeutic effects on the reducing postoperative infection and enhances osteointegration of intra‐osseous implants in diabetic rat models. The proposed strategy opens up a promising opportunity for repurposing metals with intrinsic enzyme‐like activity for the goal of enhancing the osteointegration of devices with orthopedic and dental applications among diabetic patients. [ABSTRACT FROM AUTHOR]

GRAPH Corrected figure for original Figure S17. GRAPH Corrected figure of original Figure 2d. Safeguarding Osteointegration in Diabetic Patients: A Potent "Chain Armor" Coating for Scavenging ROS and Macrophage Reprogramming in a Microenvironment-Responsive Manner. [Extracted from the article]

Abiotic stresses usually affect plant growth and development, indirectly or directly causing crop production reduction and even plant death. To survive, plants utilize different mechanisms to adapt themselves to continuously changing surrounding environmental stresses. Homeodomain‐leucine zipper (HD‐Zip) transcription factors are unique to the plant kingdom and divided into four different subfamilies (HD‐Zip I∼IV). Many HD‐Zip I members have been shown to play critical roles in the regulation of plant developmental processes, signaling networks and responses to environmental stresses. This review focuses on the role of HD‐Zip I transcription factors in plant responses to various abiotic stresses, including abscisic acid‐mediated stress, drought and cold stress, oxidative stress, helping to identify the potential regulatory mechanisms that alleviate abiotic stress in plants. [ABSTRACT FROM AUTHOR]

Abstract: Improvement in the clinical outcome of human cancers requires characterization of the genetic alterations underlying their pathogenesis. Large‐scale genomic and transcriptomic characterization of papillary thyroid carcinomas (PTCs) in Western populations has revealed multiple oncogenic drivers which are essential for understanding pathogenic mechanisms of this disease, while, so far, the genetic landscape in Chinese patients with PTC remains uncharacterized. Here, we conducted a large‐scale genetic analysis of PTCs from patients in China to determine the mutational landscape of this cancer. By performing targeted DNA amplicon and targeted RNA deep‐sequencing, we elucidated the landscape of somatic genetic alterations in 355 Chinese patients with PTC. A total of 88.7% of PTCs were found to harbor at least one candidate oncogenic driver genetic alteration. Among them, around 72.4% of the cases carried BRAF mutations; 2.8% of cases harbored RAS mutations; and 13.8% of cases were characterized with in‐frame gene fusions, including seven newly identified kinase gene fusions. TERT promoter mutations were likely to occur in a sub‐clonal manner in our PTC cohort. The prevalence of somatic genetic alterations in PTC was significantly different between our Chinese cohort and TCGA datasets for American patients. Additionally, combined analyses of genetic alterations and clinicopathologic features demonstrated that kinase gene fusion was associated with younger age at diagnosis, larger tumor size, and lymph node metastasis in PTC. With the analyses of DNA rearrangement sites of RET gene fusions in PTC, signatures of chromosome translocations related to RET fusion events were also depicted. Collectively, our results provide fundamental insight into the pathogenesis of PTC in the Chinese population. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

As a new class of crystalline nanoporous materials, metal-organic frameworks (MOFs) have recently been used for biomedical applications due to their large surface area, high porosity, and theoretically infinite structures. To improve the biological performance of titanium, MOF films were applied to surface modification of titanium. Zn-based MOF films composed of zeolitic imidazolate framework-8 (ZIF-8) crystals with nanoscale and microscale sizes (nanoZIF-8 and microZIF-8) were prepared on porous titanium surfaces by hydrothermal and solvothermal methods, respectively. The ZIF-8 films were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The nanoZIF-8 film exhibited good biocompatibility, whereas the microZIF-8 film showed obvious cytotoxicity to MG63 cells. Compared to pure titanium and alkali- and heat-treated porous titanium, the nanoZIF-8 film not only enhanced alkaline phosphatase (ALP) activity, extracellular matrix mineralization, and expression of osteogenic genes (ALP, Runx2) in MG63 cells but also inhibited the growth of Streptococcus mutans. These results indicate that MOF films or coatings may be promising candidates for bone tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 834-846, 2017. [ABSTRACT FROM AUTHOR]

The angiotensin II type 1 receptor ( AT1R) blocker losartan ameliorates rheumatoid arthritis ( RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis ( AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate ( MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10−8-10−5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum ( FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats. [ABSTRACT FROM AUTHOR]