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.

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.

基于LS-DYNA的不同装药量对爆破振动效应的影响研究

由于爆破活动的复杂性,很难通过工程试验进行爆破振动效应研究。运用数值模拟计算的方法对爆破振动效应及其危害进行相关研究。结合吴庄铁矿的相关数据,运用ANSYS/LS-DYNA有限元程序模拟1 000 kg、1 500 kg、2 000 kg及3 000 kg等4种装药量情况下的爆破对地层岩体的振动效应,通过分析得到爆破振速衰减变化以及其应力的变化规律,得出本次爆破生产作业最大装药量为1 500 kg时最为合理;同时该模型模拟结果与吴庄铁矿实际生产爆破计划基本吻合,说明该模型的构建较为成功。模拟结果可以较真实地反映出该铁矿爆破时的爆破振动效应对矿区周边建筑物的影响。

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LS-DYNA的深孔分段爆破模拟优化研究

本研究以某钨矿深孔分段爆破成井项目为背景,利用LS-DYNA非线性动力有限元软件进行了深孔一次凿岩分段爆破条件下的段高参数优化模拟。通过比较不同掏槽孔微差起爆顺序,发现相邻炮孔同时起爆的掏槽效果优于对向炮孔同时起爆的效果。研究结果揭示了随着段高的增加,装药量及岩石的炸药单耗同步增加。特别在2.3 m和2.6 m段高成井时,不仅成井效果较好,而且飞石产生较少。工业试验进一步验证了模拟结果的准确性,证实采用2.6 m分段高度进行分段爆破在实际工程中能够达到较佳的爆破效果。这些研究成果不仅为该钨矿深孔分段爆破成井项目提供了科学依据,同时也为类似工程提供了宝贵的经验和方法参考。

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.

基于LS-DYNA二次开发的AlNi合金弹丸对单层靶的撞击特性研究

基于塑性功温升原理对Johnson Cook材料模型中的温度项进行了简化,并加入了冲击反应材料化学反应模型,基于LS-DYNA平台下的二次开发功能编写得到适用于冲击反应材料的本构模型。建立了弹丸撞击单层防护结构的仿真模型并分别研究了普通材料和冲击反应材料的毁伤特性。得到了不同撞击参数下冲击反应材料和普通金属弹丸对单层靶板的毁伤规律。

The"4+4"Medical Doctor(MD)Pilot Program at PUMC:Implementation,Performance,and Prospects

Peking Union Medical College(PUMC)launched the"4+4"Medical Doctor(MD)pilot program in 2018,admitting students with non-medical backgrounds from top universities,aligning with national medical talent training policies to foster diverse and eager learners in medicine.On the occasion of the graduation of the first class of the"4+4"MD pilot class at PUMC in 2023,we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students,faculties,and management staff of the pilot class.This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting,and demonstrates the achievements of the pilot class in terms of student academic background structure,knowledge acquisition and skill learning,scientific research ability,and course evaluation.The results indicated that the pilot class had met the national demand for the"Medicine+X"talent training model.More specifically,with a diverse academic backgrounds,the pilot class graduates had academic levels comparable to the eight-year medical education graduates,and their scientific research abilities were satisfactory.The pilot program at PUMC will optimize the curriculum setting,strengthen the construction of faculty,learning resources,and teaching facilities,and reform the academic evaluation methods,thus deepening the reform of medical education and improving the"4+4"MD program as a novel medical education model.

Recent Progress in Reinforcement Learning and Adaptive Dynamic Programming for Advanced Control Applications

Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis

BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

Adaptive Optimal Discrete-Time Output-Feedback Using an Internal Model Principle and Adaptive Dynamic Programming

In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.

基于LS-DYNA的ECC管桩的抗冲击性能分析

为研究工程水泥基复合材料(Engineering Cementitious Composite,ECC)管桩的抗冲击性能,采用Ansys/LS-DYNA对管桩受竖向落锤冲击作用进行模拟。基于静态拉压试验和动态压缩试验获得关键参数,建立ECC管桩的HJC(Holmquist-Johnson-Cook)本构模型,通过霍普金森压杆试验(Split Hopkinson Pressure Bar,SHPB)验证有限元模型的正确性。对不同锤体质量和冲击速度组合的管桩模型进行参数化分析,得到管桩在不同冲击能量下的位移、能量时程曲线和有效塑性应变图等动力响应。结果表明:在竖向冲击作用下,ECC管桩的最大残余变形只有高强混凝土(High-Strength Concrete,HC)管桩的66.0%,最小残余变形仅为HC管桩的13.7%;且ECC管桩释放的变形能占比平均为HC管桩的6.26倍。表明ECC管桩较HC管桩有更好的抗损伤能力和弹性恢复能力。

Recovery after ischemic stroke:Effects of FuekFone home-based program on upper limb and cognitive function

Objectives:This study aimed to explore the effects of the“FuekFone(F.F.)home-based program”on the upper limb and cognitive function of ischemic stroke patients after discharge.Methods:A single group pre-and post-test design was conducted.A total of 40 patients with recovery after ischemic stroke were recruited from two university hospitals in Thailand.The study was conducted between June 2022 and January 2023.Participants underwent a six-week“F.F.home-based program,”which combined an upper limb and cognitive function rehabilitation device with Android games,including stationary barrel,adventure walk,adventure stroll,sliding barrel,sauce squeeze,and cut objects.Each game has different difficulty levels.Patients can perform corresponding exercises through the games according to their conditions under the guidance of medical staff.The patients played for 24 min per time,4 min each game,three days a week.The second week,let the patients play games for 30 min per time,5 min each game,3 days a week.Then,in the 3e6 weeks,let the patients play games for 1 h per time,10 min each game,5 days a week.At the pre-and post-intervention,the Thai version of the National Institutes of Health Stroke Scale(NIHSS),the Motor Assessment Scale,and the Montreal Cognitive Assessment(MoCA score)were administered to patients at discharge and at 2,4,and 6 weeksafter discharge,and the results were compared.Results:All participants completed this program.Participants had statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 2,4,and 6 weeks after discharge(P<0.001).In the comparison of upper limb function and cognitive function at each of the study times,we found statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 4,and 6 weeks after discharge when compared to after discharge and 2 weeks after discharge,respectively(P<0.05).Conclusions:Continuing care of patients post-stroke after discharge from hospital,such as F.F.homebased program should be applied at home to enhance upper limb and cognitive function.