ONECUT2高表达介导胃癌复发患者5-FU化疗耐药

目的:探究One cut结构域家族成员2(ONECUT2)是否可以作为对5-FU耐药的胃癌复发患者的治疗靶点。方法:利用癌症基因组图谱(TCGA)数据库分析ONECUT2基因在胃癌患者及胃癌复发患者的表达情况。利用基因集富集分析(GSEA)评估TCGA数据库中ONECUT2表达量与药物代谢相关生物学过程的相关性。利用CCK-8细胞毒性实验评估胃癌细胞敲低或过表达ONECUT2对5-FU的耐药情况。分析30例胃癌术后复发患者ONECUT2表达量与5-FU治疗效果的相关性。结果:TCGA数据库分析显示,在经受过化疗且复发的胃癌患者中,ONECUT2高表达的患者无病间隔期(disease-free interval,DFI)更短。GSEA分析结果表明,ONECUT2高表达与异生药物代谢通路呈正相关,这提示可能与胃癌患者的耐药相关。体外实验中,敲低ONECUT2降低胃癌细胞对5-FU的半数抑制浓度(IC_(50))值;反之,过表达ONECUT2增加细胞对5-FU的IC_(50)值。30例胃癌复发患者对5-FU的药物敏感性与ONECUT2表达量相关。结论:胃癌复发患者的ONECUT2表达量更高,ONECUT2高表达与胃癌复发患者的5-FU耐药相关,可能是潜在的治疗靶点。

冠菌素诱导橡胶树次生乳管分化的形成层细胞CUT&Tag文库构建和初步分析

CUT&Tag技术是一种研究蛋白质-DNA互作的新方法,使用超高活性的新型pG-Tn5转座酶,在抗体引导下精准靶向切割目的蛋白附近的DNA序列,从而进行cDNA建库和测序分析。此技术在人类和动物研究中应用广泛,由于植物细胞结构特殊,该技术在植物研究中应用较少。在前期研究中,我们发现组蛋白乙酰化修饰参与茉莉酸诱导橡胶树次生乳管分化的调控,但其分子机制尚未阐明。本研究利用冠菌素(COR)诱导橡胶树萌条维管形成层分化次生乳管的实验系统,通过酶解法获取高质量的形成层区细胞原生质体,使用组蛋白H3乙酰化修饰抗体对次生乳管分化过程中发生组蛋白乙酰化修饰的区域进行原位识别,采用CUT&Tag技术成功构建COR处理橡胶树树皮形成层细胞的cDNA文库。对构建cDNA文库进行质检和测序分析,发现文库质量较好,并通过差异基因的GO和KEGG富集分析,发现生长素、类黄酮代谢和蛋白质泛素化等相关基因得到富集。本研究结果为使用CUT&Tag技术构建植物组织的cDNA文库提供操作方法,为解析组蛋白乙酰化修饰调控橡胶树次生乳管分化的分子机制提供理论基础。

Patient satisfaction and follow-up adherence to glaucoma case management clinic in China

AIM:To assess glaucoma patient satisfaction and follow-up adherence in case management and identify associated predictors to improve healthcare quality and patient outcomes.METHODS:In this cross-sectional study,a total of 119 patients completed a Patient Satisfaction Questionnaire-18 and a sociodemographic questionnaire.Clinical data was obtained from the case management system.Follow-up adherence was defined as completing each follow-up within±30d of the scheduled time set by ophthalmologists during the study period.RESULTS:Average satisfaction scored 78.65±7,with an average of 4.39±0.58 across the seven dimensions.Age negatively correlated with satisfaction(P=0.008),whilst patients with follow-up duration of 2 or more years reported higher satisfaction(P=0.045).Multivariate logistics regression analysis revealed that longer follow-up durations were associated with lower follow-up adherence(OR=0.97,95%CI,0.95-1.00,P=0.044).Additionally,patients with suspected glaucoma(OR=2.72,95%CI,1.03-7.20,P=0.044)and those with an annual income over 100000 Chinese yuan demonstrated higher adherence(OR=5.57,95%CI,1.00-30.89,P=0.049).CONCLUSION:The case management model proves effective for glaucoma patients,with positive adherence rates.The implementation of this model can be optimized in the future based on the identified factors and extended to glaucoma patients in more hospitals.

Instability mechanism of mining roadway passing through fault at different angles in kilometre-deep mine and control measures of roof cutting and NPR cables

The angle α between the fault strike and the axial direction of the roadway produces different damage characteristics. In this paper, the research methodology includes theoretical analyses, numerical simulations and field experiments in the context of the Daqiang coal mine located in Shenyang, China. The stability control countermeasure of "pre-splitting cutting roof + NPR anchor cable"(PSCR-NPR) is simultaneously proposed. According to the different deformation characteristics of the roadway, the faults are innovatively classified into three types, with α of type I being 0°-30°, α of type II being 30°-60°, and α of type III being 60°-90°. The full-cycle stress evolution paths during mining roadway traverses across different types of faults are investigated by numerical simulation. Different pinch angles α lead to high stress concentration areas at different locations in the surrounding rock. The non-uniform stress field formed in the shallow surrounding rock is an important reason for the instability of the roadway. The pre-cracked cut top shifted the high stress region to the deep rock mass and formed a low stress region in the shallow rock mass. The high prestressing NPR anchor cable transforms the non-uniform stress field of the shallow surrounding rock into a uniform stress field. PSCR-NPR is applied in the fault-through roadway of Daqiang mine. The low stress area of the surrounding rock was enlarged by 3-7 times, and the cumulative convergence was reduced by 45%-50%. It provides a reference for the stability control of the deep fault-through mining roadway.

Hole cleaning evaluation and installation spacing optimization of cuttings bed remover in extended-reach drilling

In extended-reach or long-horizontal drilling,cuttings usually deposit at the bottom of the annulus.Once cuttings accumulate to a certain thickness,complex problems such as excessive torque and drag,tubing buckling,and pipe stuck probably occur,which results in a lot of non-productive time and remedial operations.Cuttings bed remover can efficiently destroy deposited cuttings in time through hydraulic and mechanical stirring effects.This paper aims to build a method for hole cleaning evaluation and installation spacing optimization of cuttings bed remover to improve the wellbore cleaning effect.Firstly,a Computational Fluid Dynamics approach with Eulerian—Eulerian multiphase model was utilized to investigate the mechanism of cuttings transportation,and a new type of cuttings bed remover was designed.Next,an evaluation method of hole cleaning effect of remover was established.After that,the effects of several drilling parameters on hole cleaning including flow rate of drilling fluid,rotational speed of drillpipe,rate of penetration,wellbore size,rheological property of drilling fluid,and remover eccentricity on the performance of cuttings bed remover were investigated.The results demonstrate that the new type of remover with streamline blade performs better than conventional removers.The efficiency of hole cleaning is greatly improved by increasing the rotational speed of drillpipe,flow rate of drilling fluid,remover eccentricity,and 6 rpm Fann dial reading for drilling fluid.While higher rate of penetration and large wellbore size result in worse hole cleaning.These findings can serve as an important guide for the structure optimization design of cuttings bed remover and installation spacing of removers.

Loss to Specialized Cardiology Follow-Up in Adults Living with Congenital Heart Disease

Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care centers.Much less is understood about the loss to follow-up(LTF)after a successful transition.This is critical too,as patients lost to specialised care are more likely to experience mor-bidity and premature mortality.Aims:To understand the prevalence and reasons for loss to follow-up(LTF)at a large Australian Adult Congenital Heart Disease(ACHD)centre.Methods:Patients with moderate or highly complex CHD and gaps in care of>3 years(defined as LTF)were identified from a comprehensive ACHD data-base.Structured telephone interviews examined current care and barriers to clinic attendance.Results:Overall,407(22%)of ACHD patients(n=1842)were LTF.The mean age at LTF was 31(SD 11.5)years and 54%were male;311(76%)were uncontactable.Compared to adults seen regularly,lost patients were younger,with a greater socio-economic disadvantage,and had less complex CHD(p<0.05 for all).We interviewed 59 patients(14%).The top 3 responses for care absences were“feeling well”(61%),losing track of time(36%),and not needing fol-low-up care(25%).Conclusions:A large proportion of the ACHD population becomes lost to specialised cardiac care,even after a successful transition.This Australian study reports younger age,moderate complexity defects,and socio-economic disadvantage as predictive of loss to follow-up.This study highlights the need for novel approaches to patient-centered service delivery even beyond the age of transition and resources to maintain patient engagement within the ACHD service.

Yield and Nutritive Values of Semi- and Non-Fall Dormant Alfalfa Cultivars under Late-Cutting Schedule in California’s Central Valley

California is one of the major alfalfa (Medicago sativa L) forage-producing states in the U.S, but its production area has decreased significantly in the last couple of decades. Selection of cultivars with high yield and nutritive value under late-cutting schedule strategy may help identify cultivars that growers can use to maximize yield while maintaining area for sustainable alfalfa production, but there is little information on this strategy. A field study was conducted to determine cumulative dry matter (DM) and nutritive values of 20 semi- and non-fall dormant (FD) ratings (FD 7 and FD 8 - 10, respectively) cultivars under 35-day cut in California’s Central Valley in 2020-2022. Seasonal cumulative DM yields ranged from 6.8 in 2020 to 37.0 Mg·ha−1 in 2021. Four FD 8 - 9 cultivars were the highest yielding with 3-yrs avg. DM greater than the lowest yielding lines by 46%. FD 7 cultivar “715RR” produced the highest crude protein (CP: 240 g·Kg−1) while FD 8 cultivar “HVX840RR” resulted in the highest neutral detergent fiber digestibility (NDFD: 484 g·Kg−1, 7% greater than the top yielding cultivars) but with DM yield intermediate. Yields and NDFD correlated positively but weakly indicating some semi- and non-FD cultivars performing similarly. These results suggest that selecting high yielding cultivars under 35-day cutting schedule strategy can be used as a tool to help growers to maximize yield while achieving good quality forages for sustainable alfalfa production in California’s Central Valley.

Essential role of postoperative follow-up in the management of clear cell sarcoma

Clear cell sarcoma(CCS)is a rare melanocytic soft tissue sarcoma known for itspropensity to metastasize to the lymph nodes and typically has an unfavorableprognosis.Currently,surgical resection is the primary treatment for localizedCCS,while radiotherapy and chemotherapy are preferred for metastatic cases.The roles of adjuvant chemotherapy,radiotherapy,and lymph node dissection arecontroversial.Although immunotherapy has emerged as a promising avenue inCCS treatment research,there are no established clinical standards for postoperativefollow-up.This editorial discusses a recent article by Liu et al,with afocus on current diagnostic modalities,treatment approaches,and the challengingprognosis associated with CCS.Our aim is to underscore the importance of longtermpatient follow-up in CCS management.

Unraveling engineering disturbance effects on deformation in red-bed mudstone railway cuttings:incorporating crack-facilitated moisture diffusion

Red-bed mudstone, prevalent in southwest China, poses a formidable challenge due to its hydrophilic clay minerals, resulting in expansion, deformation, and cracking upon exposure to moisture. This study addresses uplift deformation disasters in high-speed railways by employing a moisture diffusion-deformation-fracture coupling model based on the finite-discrete element method(FDEM). The model integrates the influence of cracks on moisture diffusion. The investigation into various excavation depths reveals a direct correlation between depth and the formation of tensile cracks at the bottom of the railway cutting. These cracks expedite moisture migration, significantly impacting the temporal and spatial evolution of the moisture field. Additionally, crack expansion dominates hygroscopic deformation, with the lateral coordinate of the crack zone determining peak vertical displacement. Furthermore, key factors influencing deformation in railway cuttings, including the swelling factor and initial moisture content at the bottom of the cutting, are explored. The number of tensile and shear cracks increases with greater excavation depth, particularly concerning shear cracks. Higher swelling factors and initial moisture contents result in an increased total number of cracks, predominantly shear cracks. Numerical calculations provide valuable insights, offering a scientific foundation and directional guidance for the precise prevention, control, prediction, and comprehensive treatment of mudstone-related issues in high-speed railways.

Benefits of endoscopic gallbladder stenting following percutaneous transhepatic gallbladder drainage

BACKGROUND Endoscopic transpapillary gallbladder drainage is challenging because of the complexity of the procedure and high incidence of adverse events(AEs).To overcome these problems,endoscopic gallbladder stenting(EGBS)after percutaneous transhepatic gallbladder drainage(PTGBD)can be effective,as it mitigates inflammation and adhesion.AIM To examine the benefits of EGBS after PTGBD to assess its efficacy and impact on AEs.METHODS We retrospectively analyzed data from 35 patients who underwent EGBS after PTGBD at a single center between January 2016 and December 2023.The primary outcomes were technical success and AEs,and the rate of recurrent cholecystitis was evaluated.In addition,the reasons for the failure of the procedure were identified.RESULTS Among the 35 patients,the technical success rate was 77.1%and the final contrast of the cystic duct was successful in 97.1%of patients.The incidence of early AEs was relatively low(11.4%),with no instances of cystic duct perforation.The rate of recurrent cholecystitis was 3.7%,and no other biliary events were observed.CONCLUSION EGBS after PTGBD may be significantly beneficial,with a substantial success rate and minimal AEs in both short-and long-term follow-ups.

Precipitates Generation Mechanism and Surface Quality Improvement for Aluminum Alloy 6061 in Diamond Cutting

To improve the surface quality for aluminum alloy 6061(Al6061) in ultra-precision machining, we investigated the factors affecting the surface finish in single point diamond turning(SPDT)by studying influence of the precipitates generation of Al6061 on surface integrity and surface roughness.Based on the Johnson-Mehl-Avrami solid phase transformation kinetics equation, theoretical and experimental studies were conducted to build the relationship between the aging condition and the type, size and number of the precipitates for Al6061. Diamond cutting experiments were conducted to machine Al6061 samples under different aging conditions. The experimental results show that, the protruding on the chip surface is mainly Mg_(2)Si and the scratches on the machined surface mostly come from the iron-containing phase(α-, β-AlFeSi).Moreover, the generated Mg_(2)Si and α-, β-AlFeSi affect the surface integrity and the diamond turned surface roughness. Especially, the achieved surface roughness in SPDT is consistent with the variation of the number of AlFeSi and Mg_(2)Si with the medium size(more than 1 μm and less than 2 μm) in Al6061.

Assessing cutter-rock interaction during TBM tunnelling in granite:Large-scale standing rotary cutting tests and 3D DEM simulations

The widespread utilisation of tunnel boring machines(TBMs)in underground construction engineering requires a detailed investigation of the cutter-rock interaction.In this paper,we conduct a series of largescale standing rotary cutting tests on granite in conjunction with high-fidelity numerical simulations based on a particle-type discrete element method(DEM)to explore the effects of key cutting parameters on the TBM cutter performance and the distribution of cutter-rock contact stresses.The assessment results of cutter performance obtained from the cutting tests and numerical simulations reveal similar dependencies on the key cutting parameters.More specifically,the normal and rolling forces exhibit a positive correlation with penetration but are slightly influenced by the cutting radius.In contrast,the side force decreases as the cutting radius increases.Additionally,the side force shows a positive relationship with the penetration for smaller cutting radii but tends to become negative as the cutting radius increases.The cutter's relative effectiveness in rock breaking is significantly impacted by the penetration but shows little dependency on the cutting radius.Consequently,an optimal penetration is identified,leading to a low boreability index and specific energy.A combined Hertz-Weibull function is developed to fit the cutter-rock contact stress distribution obtained in DEM simulations,whereby an improved CSM(Colorado School of Mines)model is proposed by replacing the original monotonic cutting force distribution with this combined Hertz-Weibull model.The proposed model outperforms the original CSM model as demonstrated by a comparison of the estimated cutting forces with those from the tests/simulations.The findings from this work that advance our understanding of TBM cutter performance have important implications for improving the efficiency and reliability of TBM tunnelling in granite.

Long-term assessment of collagenase treatment for Dupuytren’s contracture:A 10-year follow-up study

BACKGROUND Enzymatic fasciotomy with collagenase clostridium histolyticum(CCH)has revolutionized the treatment for Dupuytren’s contracture(DC).Despite its benefits,the long-term outcomes remain unclear.This study presented a comprehensive 10-year follow-up assessment of the enduring effects of CCH on patients with DC.AIM To compare the short-term(12 wk)and long-term(10 years)outcomes on CCH treatment in patients with DC.METHODS A cohort of 45 patients was treated with CCH at the metacarpophalangeal(MCP)joint and the proximal interphalangeal(PIP)joint and underwent systematic reevaluation.The study adhered to multicenter trial protocols,and assessments were conducted at 12 wk,7 years,and 10 years post-surgery.RESULTS Thirty-seven patients completed the 10-year follow-up.At 10 years,patients treated at the PIP joint exhibited a 100%recurrence.However,patients treated at the MCP joint only showed a 50%recurrence.Patient satisfaction varied,with a lower satisfaction reported in PIP joint cases.Recurrence exceeding 20 degrees on the total passive extension deficit was observed,indicating a challenge for sustained efficacy.Significant differences were noted between outcomes at the 7-year and 10-year intervals.CONCLUSION CCH demonstrated sustained efficacy when applied to the MCP joint.However,caution is warranted for CCH treatment at the PIP joint due to a high level of recurrence and low patient satisfaction.Re-intervention is needed within a decade of treatment.

Environmental Impact Assessment Follow-Up of Seismic Survey Offshore Activities in Brazil

Follow-up of environmental impacts is an integral part of the Environmental Impact Assessment (EIA) process, closely related to the effectiveness of the instrument. EIA follow-up has been receiving a lot of interest from scientists and practitioners, though it is recognized as one of the weakest points of EIA systems globally. Also, EIA follow-up is influenced by the context, mainly in terms of the types of projects or activities and their related impacts on the environment. Therefore, the present paper is focused on the investigation of the follow-up stage applied to the activity of seismic survey coupled with offshore oil & gas exploitation in Brazil. Research was based on a qualitative approach that included document analysis and semi-structured interviews with analysts involved in EIA processes, and sought to generate evidence of effectiveness of the EIA follow-up as conducted by the Federal Environment Agency (Ibama) in order to situate the practice of follow-up in the broader context of international best practice principles. Based on the findings, it was concluded that, due to the peculiarities of offshore seismic survey, it is necessary to promote adaptations in the procedures for monitoring impacts in order to ensure proper alignment with the principles and conceptual foundations that guide EIA practice. Specifically, the timing of the execution of the activity imposes challenges for its integration into the “conventional” cycle that has guided the monitoring of the impacts in the EIA of projects.

Concurrent Two-Scale Topology Optimization of Thermoelastic Structures Using a M-VCUT Level Set Based Model of Microstructures

By analyzing the results of compliance minimization of thermoelastic structures,we observed that microstructures play an important role in this optimization problem.Then,we propose to use a multiple variable cutting(M-VCUT)level set-based model of microstructures to solve the concurrent two-scale topology optimization of thermoelastic structures.A microstructure is obtained by combining multiple virtual microstructures that are derived respectively from multiple microstructure prototypes,thus giving more diversity of microstructure and more flexibility in design optimization.The effective mechanical properties of microstructures are computed in an off-line phase by using the homogenization method,and then a mapping relationship between the design variables and the effective properties is established,which gives a data-driven model of microstructure.In the online phase,the data-driven model is used in the finite element analysis to improve the computational efficiency.The compliance minimization problem is considered,and the results of numerical examples prove that the proposed method is effective.

Ground response and failure mechanism of gob-side entry by roof cutting with hard main roof

This study is the result of long-term efforts of the authors’team to assess ground response of gob-side entry by roof cutting(GSERC)with hard main roof,aiming at scientific control for GSERC deformation.A comprehensive field measurement program was conducted to determine entry deformation,roof fracture zone,and anchor bolt(cable)loading.The results indicate that GSERC deformation presents asymmetric characteristics.The maximum convergence near roof cutting side is 458 mm during the primary use process and 1120 mm during the secondary reuse process.The entry deformation is closely associated with the primary development stage,primary use stage,and secondary reuse stage.The key block movement of roof cutting structure,a complex stress environment,and a mismatch in the supporting design scheme are the failure mechanism of GSERC.A controlling ideology for mining states,including regional and stage divisions,was proposed.Both dynamic and permanent support schemes have been implemented in the field.Engineering practice results indicate that the new support scheme can efficiently ensure long-term entry safety and could be a reliable approach for other engineering practices.

Cutting Propagation Technique of Pennisetum purpureum Schum

[Objectives]The paper was to study the cutting propagation technique of Pennisetum purpureum Schum and to provide a technical reference for establishing an efficient cutting propagation method.[Methods]Six treatments were set up using P.purpureum cv.Guiminyin and P.purpureum cv.Guimu-1 as test materials,including 1-node oblique insertion,1-node oblique insertion+rooting powder,1-node transverse burial,2-node oblique insertion,2-node oblique insertion+rooting powder and 2-node transverse burial.The following indices were observed and determined for P.purpureum cuttings:emergence rate,rooting rate,root number,longest root length,fresh root weight,plant height,number of tillers,number of leaves,and fresh stem and leaf weight.[Results]In the 2-node cutting+rooting powder treatment,Guiminyin and Guimu-1 exhibited the highest survival rate,root growth indices,and stem and leaf growth indices,with the emergence rates of 94.29%and 90.26%,respectively.The 2-node cutting treatment followed closely behind,while the 1-node cutting treatment had the lowest indices.Under the same treatment,Guimuyin exhibited higher mean values for plant height,number of leaves,fresh stem and leaf weight,longest root length,and fresh root weight compared to Guimu-1.However,it had lower mean number of tillers,and emergence rate and rooting rate of the 1-node cutting treatment compared to Guimu-1.[Conclusions]The P.purpureum cuttings thrived in the 2-node cutting+rooting powder treatment,and the overall cutting effect of Guiminyin was superior to that of Guimu-1.

Cutting-edge Technological Innovation Outcome Displayed at 2024 Beijing Science and Technology Week

The 2024 National Science and Technology Week and Beijing Science and Technology Week opened in Shougang Park in Shijingshan District from May 25 to June 1.Under the theme of“Carrying forward the spirit of scientists and inspiring societal innovation,”this event focused on the new-generation IT technology,medical health,energy and technology,modern agriculture and intelligent manufacturing industries.

Endoscopic radial incision and cutting method for adult congenital duodenal webs:A case report

BACKGROUND Congenital duodenal webs are rare in adults and can lead to various symptoms such as nausea,vomiting,and postprandial fullness.The treatment for this disease is mostly surgical.Endoscopic treatment techniques have been developed and attempted for this disease.Endoscopic radial incision and cutting(RIC)techniques are reportedly very effective in benign anastomotic stricture.This case report highlights the effectiveness and safety of endoscopic RIC as a minimally invasive treatment for adult congenital duodenal webs.CASE SUMMARY A 23-year-old female patient with indigestion was referred to a tertiary hospital.The patient complained of postprandial fullness in the epigastric region.Previous physical examinations or blood tests indicated no abnormalities.Computed tomography revealed an eccentric broad-based delayed-enhancing mass-like lesion in the second portion of the duodenum.Endoscopy showed an enlarged gastric cavity and a significantly dilated duodenal bulb;a very small hole was observed in the distal part of the second portion,and scope passage was not possible.Gastrografin upper gastrointestinal series was performed,revealing an intraduodenal barium contrast-filled sac with a curvilinear narrow radiolucent rim,a typical"windsock"sign.Endoscopic RIC was performed on the duodenal web.The patient recovered uneventfully.Follow-up endoscopy showed a patent duodenal lumen without any residual stenosis.The patient reported complete resolution of symptoms at the 18-month follow-up.CONCLUSION Endoscopic RIC may be an effective treatment for congenital duodenal webs in adults.

Application of Fuyang Paper Cutting Art in Cultural and Creative Design from the Perspective of Rural Revitalization

The application significance of Fuyang paper cutting art in cultural and creative design from the perspective of rural revitalization was discussed,and the implementation principles and specific practices of applying the elements and techniques of Fuyang traditional paper cutting art in cultural and creative products with local features were analyzed to provide reference for rural revitalization and development of cultural industry.