Glia-to-neuron reprogramming to the rescue?

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

Neurocircuit regeneration by extracellular matrix reprogramming

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

Programmed cell death 1 inhibitor sintilimab plus S-1 and gemcitabine for liver metastatic pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.

Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.

Perspectives of high-risk pregnant women on home care program in high-risk pregnancies: A multicenter, qualitative study

Objective:To explore the perspectives of high-risk pregnant women regarding the home care program for high-risk pregnancies.Methods:This qualitative study was conducted in a university hospital and 5 comprehensive health centers in Ahvaz,Iran,from February 2023 to July 2023.The sampling method used was purposive sampling considering the maximum possible diversity,which continued until data saturation.11 in-depth and semistructured interviews were conducted with high-risk pregnant women.Data were simultaneously analysed using Graneheim and Lundman content analysis by MAXQDA version 20 software.Results:Data analysis extracted 3 themes,12 categories,and 26 subcategories.The themes and categories were“high-risk pregnancy and related issues(pursuing treatment and paying attention to the high-risk situation by pregnant women,psychological aspect of high-risk pregnancy on pregnant women and caregivers,emotional and physical aspects of high-risk pregnancy,the consequences of high-risk pregnancy on the people around them and empowerment of high-risk pregnant women)”,“support dimension(family and community support for high-risk pregnant women)”,and“framework of program(acculturalization,means and equipment,security,manpower and the necessary arrangements for the home care)”.Conclusions:High-risk pregnancy affects various aspects of the lives of high-risk pregnant women and their families.Creating the necessary conditions for providing care at home plays a vital role in supporting high-risk pregnant women and removing related obstacles to receiving prenatal care in person.It will be especially beneficial for high-risk pregnant women in low-income areas.

Brand Early Promotion Program for Fresh Agricultural Product"Longxuhuang"

This study focuses on"Longxuhuang",a fresh agricultural product from Longtian Town in Longmen County.By establishing the objectives of brand promotion and analyzing the appropriate promotional channels,we aim to effectively position the brand,cultivate a promotional atmosphere,identify suitable channels for promotion,anticipate potential risks,and propose corresponding countermeasures.Additionally,we assess the effectiveness of the promotional strategies employed.The findings of this research will contribute to the brand promotion of enterprises and offer insights for the brand promotion of agricultural products in other regions.

Programmed cell death receptor 1 inhibitor Pembrolizumab in the treatment of advanced gastric cancer

This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice.

Granulomatosis with polyangiitis induced by the anti-programmed cell death-1 inhibitor tislelizumab:A case report

BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.

新工科背景下融合OBE-CDIO理念的“C#程序设计”课程改革创新与实践

针对当前新工科建设中面临的高职院校工程应用人才培养无法满足产业快速发展需求的现状,以江苏信息职业技术学院的“C#程序设计”课程教学改革为例进行深入分析。通过对课程内容、教学资源、学习情境以及考核评价的系统改进,探讨如何将OBE能力导向与CDIO工程实践导向教育理念融合应用于高职软件类课程改革的创新实践中,揭示了这种复合教育理念对学生综合素质和职业能力的培养带来的积极影响,为高职软件类课程改革提供了有效参考和借鉴。

基于C#语言与ArcGIS Engine 的开采沉陷预计系统开发

为了预计煤层开采引发的地表移动变形,基于极坐标系的概率积分法,借助C#语言和ArcGIS Engine组件工具库设计开发了矿区开采沉陷预计系统。开采沉陷预计系统适用于不规则形状的开采工作面,能够对开采区域地表各点不同开采时间后的下沉、水平移动、水平变形、倾斜、曲率进行预计,并对预计结果进行后处理,绘制地表移动变形云图。以陕西省某矿308工作面开采为例,根据工作面的开采条件、地层岩性等特征选取概率积分参数并代入本系统进行地表移动变形预计,将结果与实测地表移动变形进行对比分析。结果表明:使用该系统预计的地表下沉值与实测下沉值的相对误差小于10%,且下沉盆地形态与实际基本吻合,该系统的预计结果较为可靠,对矿区的开采沉陷预计具有一定的适用性。

融入“双主体”教育思想的C#课程线上线下混合式教学研究

本文以C#课程线上线下混合式教学为例,设定课程教学目标,选取合适教学模式,依托现有线下线上课程教学资源,融入“双主体”教育思想,分线上线下两类以及各类两个阶段进行混合式教学活动设计,探索在混合式教学过程中发挥教师、学生“双主体”能动性,激发学生主体在学习过程的主动性、积极性与创造性,以及发挥教师主体引导、启发、监控教学过程的主导作用,努力达成教师教授最优化与学生学习最优化,以期达到更好的教学及学习效果。This article takes the mixed online and offline teaching of C Sharp courses as an example, sets course teaching objectives, selects appropriate teaching modes, relies on existing online and offline course teaching resources, integrates the “Double Main Body” education concept, and designs mixed teaching activities in two categories and two stages of online and offline, exploring the use of the “Double Main Body” initiative of teachers and students in the mixed teaching process, stimulating the initiative, enthusiasm, and creativity of students in the learning process, and exerting the leading role of teachers in guiding, inspiring, and monitoring the teaching process, striving to achieve the optimization of teacher teaching and student learning, in order to achieve better teaching and learning effects.

基于C#的最佳抵偿高程面选取软件设计与应用

规范规定建立或选择平面坐标系统的前提条件是测区内投影所引起的长度变形不大于25 mm/km。某测区公路工程施工控制网采用国家坐标系不能满足这一要求,为减小高斯投影长度变形所带来的影响,本研究选用膨胀椭球与重心坐标不变法建立工程抵偿坐标系,并基于C#语言进行抵偿坐标系最佳抵偿面选取软件设计。研究结果表明,该计算方法严密、可靠,软件计算结果快速准确,可以实现抵偿坐标计算的自动化处理,能够满足规范要求,可直接应用于工程生产。

“C#程序设计”课程思政探究

程序设计类课程是软件人才培养的重要课程。通过在“C#程序设计”课程中有效融入课程思政,潜移默化地培养学生的思政素养,引导学生树立正确的世界观、人生观、价值观,打造专业教育与思政教育的协同效应,促进学生德智体美劳全面发展。

基于OBE理念的C#编程与SQL数据库应用课程教学改革

为有效培养自动化专业学生应具备的系统分析、设计与研发能力,针对C#编程与SQL数据库应用课程存在的教学模式单一、课程内容实践不够、学生能力培养不足等问题,制定以工程意识和工程素质为核心的培养目标,以云班课教学平台为依托,探索线上线下混合式、课堂企业交叉式教学模式。基于成果导向的教学理念的理论与实践相结合的教学内容,通过项目驱动式方法改革授课方式,采用自主式、团队式相融合的方法改革实践教学,并探讨全方位多层次的考评方法,以提高学生解决复杂工程问题的能力。

基于C#+OpenGL的多探头测井井筒三维成像软件研制与应用研究

基于油水、气水等多相流实验数据和图像资料,采用C#语言结合Tao框架OpenGL研发一套适用于MAPS阵列多探头测井(以下简称“MAPS测井”)仪器的井筒流体三维成像显示(COSL-MapsView)软件。该软件可实现测井数据的直接加载,快速精确直观显示井筒内油气水的分布情况。基于图像重构对MAPS测井仪器进行了适用性研究,表明MAPS测井在水平井和大斜度井中低流量情况下的分层流中具有良好的应用效果,在高流量分散流中应用效果不佳。经验证,该软件成像效果达到了国外同等水平,对海上油气田找堵水等工程作业具有指导意义。

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

基于C#的配网在线监测系统设计与实现

中低压配网监测技术无法有效实现对各层电网运行信息的共享分析,监测可视化效果差。针对该问题,文中利用VISIO(流程图和矢量绘图软件)二次开发技术设计了一个基于C#的配网运行在线监测系统。该系统具有系统基础配置管理,包括实时数据监测、数据查询、数据分析、预警提醒管理等功能。在运行时,通过建立连接实时获取下位机终端采集的配网运行数据,使之显示于监测主页面,用户只需要通过较为简单的窗体控件控制即可实现系统基础信息配置以及在线监测。调试运行结果表明,该系统可以较好地实现远程监测与及时预警提醒,使配网运行数据得到实时利用,有效提高工作效率。

Uncertainty quantification of inverse analysis for geomaterials using probabilistic programming

Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems.In this study,a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model(ROM)and probabilistic programming.The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems.Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering.A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution.The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty.Then,a slope case was employed to demonstrate the performance of the developed framework.The results prove that the proposed framework provides a scientific,feasible,and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Pretreatment can alleviate programmed cell death in mesenchymal stem cells

In this editorial,we delved into the article titled“Cellular preconditioning and mesenchymal stem cell ferroptosis.”This groundbreaking study underscores a pivotal discovery:Ferroptosis,a type of programmed cell death,drastically reduces the viability of donor mesenchymal stem cells(MSCs)after engraftment,thereby undermining the therapeutic value of cell-based therapies.Furthermore,the article proposes that by manipulating ferroptosis mechanisms through preconditioning,we can potentially enhance the survival rate and functionality of MSCs,ultimately amplifying their therapeutic potential.Given the crucial role ferroptosis plays in shaping the therapeutic outcomes of MSCs,we deem it im-perative to further investigate the intricate interplay between programmed cell death and the therapeutic effectiveness of MSCs.