Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

AIM:To investigate immunosuppressive agents used to treat inflammatory bowel disease(IBD)in East China. METHODS:A retrospective review was conducted, involving 227 patients with IBD admitted to Sir Run Run Shaw Hospital,College of Medicine,Zhejiang University from June 2000 to December 2007.Data regarding demographic,clinical characteristics and immunosuppressants usage were analyzed. RESULTS:A total of 227 eligible patients were evaluated in this study,including 104 patients with Crohn’s disease and 123 with ulcerative colitis.Among the patients,61 had indications for immunosuppressive agents use.However,only 21 (34.4%)received immunosuppressive agents.Among the 21 patients,6(37.5%)received a subtherapeutic dose of azathioprine with no attempt to increase the dosage.Of the 20 patients that received immunosuppressive agent treatment longer than 6 mo,15 patients went into remission,four patients were not affected and one relapsed.Among these 20 patients,four patients suffered from myelotoxicity and one suffered from hepatotoxicity.CONCLUSION:Immunosuppressive agents are used less frequently to treat IBD patients from East China compared with Western countries.Monitoring immunosuppressive agent use is recommended to optimize dispensation of drugs for IBD in China.

Systematic Review and Meta-analysis:Immunosuppressive Agents for the Treatment of Primary Biliary Cholangitis

Background and aim:There are still no clinically satisfactory therapy for PBC.This study was performed to assess the safety and efficacy of IAs for the therapy of PBC.Methods:Relevant studies were identified and selected by searching PubMed,Web of Science and Cochrane Library databases.The primary outcome was defined as the need for mortality or liver transplantation.Adverse effects and liver biochemical variables were a secondary outcome.Results:Nine randomized controlled trials,involving six different treatment regimens with a total of 996 patients,were included in the analysis.On meta-analysis,IAs was not associated with a reduction in risk of mortality or liver transplantation(risk ratio[RR]:0.92,95% confidence interval[CI]:0.69-1.22,P=0.57,P=0%),and have resulted in more adverse effects(RR:1.44,95%CI:1.08-1.92,P=0.01,P=19%).Subgroup analysis showed that IAs monotherapy caused adverse effects such as diarrthea,abdominal pain,and renal insufficiency(RR:1.36,95% CI:1.01-1.82,P=0.04,P=48%).IAs therapy did not prominently improve markers of liver function except for alkaline phosphatases(weighted mean difference[WMD]:-0.38,95% CI:-0.62 to-0.14,P=0.002).Conclusions:IAs cannot reduce the risk of mortality or liver transplantation,whether in IAs monotherapy or combination therapy,and even be associated with more adverse effects.

Novel immunosuppressive agents in kidney transplantation

Excellent outcomes have been achieved in the field of renal transplantation. A significant reduction in acute rejection has been attained at many renal transplant centers using contemporary immunosuppressive, consisting of an induction agent, a calcineurin inhibitor, an antiproliferative agent plus or minus a corticosteroid. Despite improvements with these regimens, chronic allograft injury and adverse events still persist. The perfect immunosuppressive regimen would limit or eliminate calcineurin inhibitors and/or corticosteroid toxicity while providing enhanced allograft outcomes. Potential improvements to the calcineurin inhibitor class include a prolonged release tacrolimus formulation and voclosporin, a cyclosporine analog. Belatacept has shown promise as an agent to replace calcineurin inhibitors. A novel, fully-human anti-CD40 monoclonal antibody, ASKP1240, is currently enrolling patients in phase 2 trials with calcineurin minimization and avoidance regimens. Another future goal of transplant immunosuppression is effective and safe treatment of allograft rejection. Novel treatments for antibody mediated rejection include bortezomib and eculizumab. Several investigational agents are no longer being pursed in transplantation including the induction agents, efalizumab and alefacept, and maintenance agents, sotrastaurin and tofacitinib. The purpose of this review is to consolidate the published evidence of the effectiveness and safety of investigational immunosuppressive agents in renal transplant recipients.

Improvement Mechanism of Adhesion Performance of Anti-stripping Agents and Coupling Agents on Asphalt-Aggregate Interface Based on Molecular Dynamics

This study examined the mechanisms for improving the adhesion performance of the asphalt-aggregate interface with two anti-stripping agents and two coupling agents.The investigation of contact behavior between various asphalt-aggregate surfaces was conducted using molecular dynamics(MD)simulations.The interaction energy and the relative concentration distribution were employed as the parameters to analyze the enhancement mechanisms of anti-stripping agents and coupling agents on the asphalt-aggregate interface.Results indicated that the adhesion at the asphalt-aggregate interface could be strengthened by both anti-stripping agents and coupling agents.Anti-stripping agents primarily improve adhesion through the reinforcement of electrostatic attraction,while coupling agents primarily upgrade adhesion by strengthening the van der Waals.Hence,the molecular dynamics modeling and calculation techniques presented in this study can be utilized to elucidate the development mechanism of the asphalt-aggregate interface through the use of anti-stripping agents and coupling agents.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

General anesthetic agents induce neurotoxicity through astrocytes

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters.Few studies,however,have focused on the effects of general anesthetic agents on neuroglia or astrocytes.Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative,analgesic,and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction.Here,we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes,and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes,in addition to acting on the receptors on their surface,which not only affect Ca^(2+)signaling,inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes,but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes.These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons,other neuroglia,and vascular cells.In this review,we summarize how general anesthetic agents act on neurons via astrocytes,and explore potential mechanisms of action of general anesthetic agents on the nervous system.We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.

Update on the reciprocal interference between immunosuppressive therapy and gut microbiota after kidney transplantation

Gut microbiota is often modified after kidney transplantation.This principally happens in the first period after transplantation.Antibiotics and,most of all,immunosuppressive drugs are the main responsible.The relationship between immunosuppressive drugs and the gut microbiota is bilateral.From one side immunosuppressive drugs modify the gut microbiota,often generating dysbiosis;from the other side microbiota may interfere with the immunosuppressant pharmacokinetics,producing products more or less active with respect to the original drug.These phenomena have influence over the graft outcomes and clinical consequences as rejections,infections,diarrhea may be caused by the dysbiotic condition.Corticosteroids,calcineurin inhibitors such as tacrolimus and cyclosporine,mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known.In contrast is well known how the gut microbiota may interfere with glucocorticoids,which may be transformed into androgens.Tacrolimus may be transformed by microbiota into a product called M1 that is 15-fold less active with respect to tacrolimus.The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glucuronidase,may be transformed into the inactive product.

Near-Infrared Fluorescence Imaging Contrast Agents for Clinical Research: Limitations and Alternatives

Introduction: Near-infrared fluorescence imaging is a technique that will establish itself in the short term at the international level because it is recognized for its potential to improve the performance of surgical interventions, its moderate investment and operating costs and its portability. Although the technology is now mature, there is currently the problem of the availability of contrast agents to be injected IV. The aim of this methodology article is to propose an alternative solution to the need for contrast agents for clinical research, particularly in oncology. Methodology: They consist of coupling a fluorescent marker in the form of an NHS derivative, such as IR DYE manufactured in compliance with GMP, with therapeutic monoclonal antibodies having marketing authorization for molecular imaging. For a given antibody, the marking procedure must be the subject of a validation file on the final preparation filtered on a sterilizing membrane at 0.22 μm. Once the procedure has been validated, it would be unnecessary to repeat the tests before each clinical research examination. A check of the marking by thin-layer chromatography (TLC) and place it in a sample bank at +4˚C for 1 month of each injected formulation would be sufficient for additional tests if necessary. Conclusion: Molecular near-infrared fluorescence imaging is experiencing development, the process of which could be accelerated by greater availability of clinical contrast agents. Alternative solutions are therefore necessary to promote clinical research in this area. These methods must be shared to make it easier for researchers.

Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

Gastric signet-ring cell carcinoma(GSRCC)is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis.Studies have shown that early GSRCC has a good prognosis,while advanced GSRCC is insensitive to radiotherapy,chemotherapy or immune checkpoint blockade therapy.With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry,more detailed atlas of tumor microenvironment(TME)in GSRCC and its association with prognosis could be investigated extensively.Recently,two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME,manifested as highly immunosuppressive,leading to high immune escape.The TME of advanced GSRCC was enriched for immunosuppressive factors,including the loss of CXCL13+-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells.In addition,GSRCC was mainly infiltrated by follicular B cells.The increased proportion of SRCC was accompanied by a decrease in mucosaassociated lymphoid tissue-derived B cells and a significant increase in follicular B cells,which may be one of the reasons for the poor prognosis of GSRCC.By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism,more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.

Effects of virtual agents on interaction efficiency and environmental immersion in MR environments

Background Physical entity interactions in mixed reality(MR)environments aim to harness human capabilities in manipulating physical objects,thereby enhancing virtual environment(VEs)functionality.In MR,a common strategy is to use virtual agents as substitutes for physical entities,balancing interaction efficiency with environmental immersion.However,the impact of virtual agent size and form on interaction performance remains unclear.Methods Two experiments were conducted to explore how virtual agent size and form affect interaction performance,immersion,and preference in MR environments.The first experiment assessed five virtual agent sizes(25%,50%,75%,100%,and 125%of physical size).The second experiment tested four types of frames(no frame,consistent frame,half frame,and surrounding frame)across all agent sizes.Participants,utilizing a head mounted display,performed tasks involving moving cups,typing words,and using a mouse.They completed questionnaires assessing aspects such as the virtual environment effects,interaction effects,collision concerns,and preferences.Results Results from the first experiment revealed that agents matching physical object size produced the best overall performance.The second experiment demonstrated that consistent framing notably enhances interaction accuracy and speed but reduces immersion.To balance efficiency and immersion,frameless agents matching physical object sizes were deemed optimal.Conclusions Virtual agents matching physical entity sizes enhance user experience and interaction performance.Conversely,familiar frames from 2D interfaces detrimentally affect interaction and immersion in virtual spaces.This study provides valuable insights for the future development of MR systems.

Effectiveness of Chromated Copper Arsenate against Deteriorating Agents of Eucalyptus Poles and Posts in Four Eco-Regions in Kenya

Previous studies done elsewhere have shown that Eucalyptus poles treated with chromated copper arsenate (CCA) can last over 30 years. Kenya is exceptional because in some eco-regions, the Eucalyptus poles’ life span has greatly reduced to 5 years. The current study was designed to evaluate wood deteriorating agents of CCA-treated Eucalyptus poles and variability in four eco-regions of Kenya, namely, dryland, coastal, highland and humid lake. A total of 360 Eucalyptus pole samples were used for this experiment. Three CCA treatments were used to treat transmission poles at 20 kg/cm3 fencing posts samples at 6 kg/cm3, and a control group. Results indicated that termites and wood-decay fungi attacks caused wood deterioration in the four eco-regions. The proportion of power transmission pole degradation by wood deteriorating agents varied across eco-regions, between treatments and control and between time after treatments. Dryland eco-regions had the highest termite-related degradation (41.82%) while wood-decay fungi attack was highest in the highland eco-regions (9.20%). Samples treated with 6 kg/cm3 recorded the lowest level of wood deterioration, manifested by minimal superficial termite and wood-decay fungi attack. Samples treated with 20 kg/cm3 were characterized by moderate termite and wood-decay fungi attacks observed around the heartwood region, unlike sapwood. This study concluded that the deterioration of Eucalyptus CCA-treated poles is a question of climatic variability and hence, to increase the poles’ lifespan, CCA treatment should be tailored according to the characteristics of the ecoregion of use. Further investigations will inform the diversity of termites and decay-fungi across different eco-regions.

Factors Influencing Compliance with Safe Handling Requirements of Anticancer Agents by Nurses in a Tertiary Hospital-A Secondary Publication

Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.

Travel Agents Around the World Praising the Trip to China

Foreign tourists'trips to China recently reached a new height,both online and offline.Travel agents around the world also made trips to China,generating more thoughts for the development of new routes and the design of innovative tourist products,and contributing to the development of China's inbound tourism.

Effects of Water-retaining Agents on Growth, Development, Yield and Quality of Soybean under Drought Stress

[Objectives]The paper was to explore the effects of different doses of water-retaining agent on the growth and development indicators,yield and quality of soybean plants subjected to drought stress.[Methods]The effects of drought stress(MDS)and drought stress with low(MDS-L),medium(MDS-M)and high doses(MDS-H)of the water-retaining agent on the growth and development indicators,root activity,MDA content,antioxidant enzyme activity,yield and quality of soybean were studied by field plot test,with the normal water supply serving as the control(CK).[Results]In response to drought stress,the plant height,stem diameter,and yield of soybean exhibited a notable decline.Additionally,the contents of protein,fat,linoleic acid,and linolenic acid in seeds demonstrated a significant reduction.Conversely,the root activity and antioxidant enzyme activity exhibited a noticeable decline,while the MDA content exhibited an increase.The application of varying doses of the water-retaining agent was found to significantly enhance soybean growth,stimulate root activity,and elevate antioxidant enzyme activity,while concurrently reducing MDA content.The observed effects were found to be dose-dependent,with the greatest effects observed at the highest dose.In comparison to MDS,the yields of soybean in the MDS-L,MDS-M,and MDS-H treatments exhibited a 18.38%,25.58%,and 46.26%increase,respectively.Additionally,the content of protein,fat,linoleic acid,and linolenic acid in seeds demonstrated a notable enhancement.[Conclusions]The application of the water-retaining agent has been demonstrated to significantly promote the growth of soybean plants under conditions of drought stress,resulting in an improvement in both the yield and the quality of the soybean crop.The recommended dosage of the water-retaining agent is 3.3 kg/667 m 2.

Optimizing Grey Wolf Optimization: A Novel Agents’ Positions Updating Technique for Enhanced Efficiency and Performance

Grey Wolf Optimization (GWO) is a nature-inspired metaheuristic algorithm that has gained popularity for solving optimization problems. In GWO, the success of the algorithm heavily relies on the efficient updating of the agents’ positions relative to the leader wolves. In this paper, we provide a brief overview of the Grey Wolf Optimization technique and its significance in solving complex optimization problems. Building upon the foundation of GWO, we introduce a novel technique for updating agents’ positions, which aims to enhance the algorithm’s effectiveness and efficiency. To evaluate the performance of our proposed approach, we conduct comprehensive experiments and compare the results with the original Grey Wolf Optimization technique. Our comparative analysis demonstrates that the proposed technique achieves superior optimization outcomes. These findings underscore the potential of our approach in addressing optimization challenges effectively and efficiently, making it a valuable contribution to the field of optimization algorithms.

Anti-Cancer Agents Associated Diarrhea:Current Status and Prospects

Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.

Expansion Performance and Microstructure of High-performance Concrete using Differently Scaled MgO Agents and Mineral Powder

To investigate the assumptions proposed in this paper,the evolution law governing the strength and expansion performance of MgO and nano-MgO micro-expansive concrete in the environment of mineral powder was firstly observed in this study.Secondly,SEM,XRD,and TG-DSC microscopic tests were conducted to reveal the effects of the active mineral-powder admixture on the hydration degree and expansion performance of MgO and nano-MgO in HPC.Our experimental results successfully verified our hypothesis,which indicated that the expansion performance of macro-MgO and nano-MgO was indeed depressed by the addition of active mineral power admixtures,even though the mechanical property of concrete composites was effectively improved.Furthermore,the hydration test also demonstrated the negative interference on the mineral powders,which was induced by the expansion agents.It is found the amounts of hydrates tend to decrease because the mineral powder ratio reaches and exceeds 40%.Moreover,it is also concluded the effect of expansion agents is governed by the alkalinity cement paste,especially for the nano-MgO.In other words,the expansion performance of nano-MgO will vary more obviously with the hydration process,than MgO.The results of this study provide that effective experimental and theoretical data support the hydration-inhibition mechanism of magnesium expansive agents.

A Device to Improve Collaborative Practices of Sanitation Department Agents of a Territory: The Case of the Lamkansa District in Casablanca

The aim of this article is to strengthen and improve the collaboration between professional agents of a service that manages one of the technical processes acting on a given territory by synchronizing the spatio-temporal dimensions including all agents assembled for the task. This proposal was tested in the Lamkansa neighborhood in Casablanca, Morocco. The employed approach is based GIS resources and on systemic analysis of communication present in a territory. We were inspired by several methodological developments that carried multi-actor processes in land use planning. We focused our work on strengthening the collaboration between professionals, field agents and office agents, in the process of design and monitoring the liquid sanitation system. The device is based on geolocation and synchronous feedback of topological, geographical, and multimedia data related to the liquid sanitation network. Thanks to a geo-collaborative, participative, and motivating logic, we reduced the management costs of the network and made it faster and more efficient by equally mobilizing another type of non-specialized actors (the inhabitants). This device uses spatial and temporal dimensions to consolidate collaborative work tools through ICT and GIS technologies that thematize and exchange information collected in the field. Furthermore, this device raises great interest as it entails the concept of integration of several actors in a geo-collaborative mode while combining geomatics with communication and information sciences.