Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis

Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.

Navigating the complex terrain of hepatitis B virus reactivation in the era of Bruton tyrosine kinase inhibitors

In this editorial,we offer a summary of the risk associated with hepatitis B reactivation(HBVr)in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase(BTK)inhibitors,with insights derived from current studies.Furthermore,we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments.This framework is essential for identifying those at increased risk of HBVr,enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.

KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.

MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A

BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.

Receptor tyrosine kinase-like orphan receptor 1:A novel antitumor target in gastrointestinal cancers

Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma:New hopes on the horizon

In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

circMYO9A_006通过翻译蛋白MYO9A-208aa发挥抑制心肌细胞肥大的作用

目的:研究环状RNA MYO9A_006(circMYO9A_006)对心肌细胞肥大表型的调控作用及可能机制。方法:利用腺病毒介导在乳小鼠心室肌细胞(NMVCs)中过表达circMYO9A_006,并以腺病毒介导过表达同样带有绿色荧光蛋白标签的空载体为对照,检测NMVCs中心肌肥大相关蛋白β-肌球蛋白重链(β-MHC)、骨骼肌肌动蛋白α1(ACTA1)和心房钠尿肽(ANP)的表达。建立去氧肾上腺素(PE)诱导的乳大鼠心室肌细胞(NRVCs)肥大模型,通过鬼笔环肽染色检测过表达circMYO9A_006对NRVCs表面积的影响。双萤光素酶报告基因实验检测circMYO9A_006包含的潜在内部核糖体进入位点(IRES)的活性。通过Western blot实验检测circMYO9A_006翻译蛋白MYO9A-208aa及其在细胞内分布情况。分别制备circMYO9A_006-ORF(直接表达MYO9A-208aa)和circMYO9A_006-ATG-mut(不能表达MYO9A-208aa)重组病毒,以空载体病毒和circMYO9A_006重组病毒分别感染NRVCs,检测circMYO9A_006翻译蛋白MYO9A-208aa对心肌细胞肥大表型的特异调节作用。结果:利用腺病毒可在NMVCs中有效介导circMYO9A_006过表达。过表达circMYO9A_006可显著抑制NMVCs中心肌肥大相关蛋白的表达(P<0.01),并显著抑制PE诱导的NRVCs中心肌肥大相关蛋白的表达和细胞表面积的增加(P<0.05)。双萤光素酶报告基因实验结果提示,circMYO9A_006包含的2个IRES均具有活性。Western blot检测结果显示,在NRVCs中过表达circMYO9A_006可翻译预期大小为28 kD的MYO9A-208aa蛋白,并主要分布于细胞质中。过表达MYO9A-208aa和circMYO9A_006可一致地抑制NRVCs心肌肥大相关蛋白表达(P<0.01),并可逆转PE诱导的NRVCs肥大反应(P<0.05);而过表达circMYO9A_006-ATG-mut没有抑制NRVCs肥大的作用。结论:circMYO9A_006通过翻译蛋白MYO9A-208aa发挥抑制心肌细胞肥大的作用。

构式语法框架下清涧方言“圪AA的”状态形容词研究

陕北晋语清涧方言中“圪AA的”状态形容词有180多个且在日常生活中使用频繁,按照构式语法属于四字格构式。形态上,该构式中A可以是形容词、动词和拟声词。“圪AA的”表达式一部分是通过其对应的“A”式“圪A”式、“AA的”式经重叠、加缀等形态变化生成,一部分是通过给“圪AA的”构式填充A后再将其重叠的结果。句法上,该构式可以在句中作谓语、定语、补语和状语,不受单音节否定词修饰,但可以用在“不/没说”含有对比的否定句中。该构式的基本义为描绘性,其语义和语用内涵包括“极致性”语义量值、“消极/负面性”立场态度偏向和“口语性”语体色彩。

Tyrosine kinase inhibitors and human epidermal growth factor receptor-2 positive breast cancer

The body of evidence investigating human epidermal growth factor receptor-2(HER2)directed therapy in patients with breast cancer(BC)has been growing within the last decade.Recently,the use of tyrosine kinase inhibitors(TKIs)has been of particular interest in the treatment of human malignancies.This literature commentary is intended to highlight the most recent findings associated with the widely-studied TKI agents and their clinical significance in improving the outcomes of HER2 positive BC.

Rituximab combined with Bruton tyrosine kinase inhibitor to treat elderly diffuse large B-cell lymphoma patients: Two case reports

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHLs.This report aims to explore the efficacy and safety of rituximab combined with Bruton tyrosine kinase inhibitors(BTKis)in the treatment of elderly patients with DLBCL.CASE SUMMARY The clinical data of two elderly patients with DLBCL who received rituximab combined with BTKi in our hospital were retrospectively analyzed,and the literature was reviewed.The patients were treated with chemotherapy using the R-miniCHOP regimen for two courses.Then,they received rituximab in combination with BTKi.CONCLUSION The treatment experience in these cases demonstrates the potential efficacy of rituximab combined with BTKi to treat elderly DLBCL patients,thus providing a new treatment strategy.

Effect of a novel tyrosine kinase inhibitor nintedanib on bFGF and VEGF concentrations in a rabbit retinal vein occlusion model

AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.METHODS:After a laser induced rabbit retinal vein occlusion(RVO)model was made,0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control.Intracameral samples were taken on the day before laser treatment and days 1,3,7,14,21,and 28 after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to test the bFGF and VEGF-A concentrations in the aqueous humor.RESULTS:Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes.In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day.After nintadanib injection in the study eye,both bFGF and VEGF-A showed a significant reduction on the 4th day(7th day after laser treatment)when compared to the control eye,and kept on low level in the following several weeks.CONCLUSION:Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent,which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.

基于AA-UNet的肝硬化辅助诊断系统

为准确地提取高频肝脏超声图像中的肝包膜,本文采用注意力门和空洞空间金字塔池化UNet(Attention gates and Atrous spatial pyramidal pooling UNet,AA-UNet)分割算法,对高频肝脏超声图像中的肝包膜进行识别,并根据肝包膜的物理形状判断肝硬化程度。首先,将数据增强后的高频肝脏超声图像送入网络模型进行训练;其次,将训练好的模型部署到肝硬化辅助诊断系统。实验结果表明,肝硬化辅助诊断系统能有效识别肝包膜区域并判断肝硬化程度。

日粮中添加琥珀酸对AA肉鸡生产性能和肠道健康的影响

试验旨在探究日粮中添加琥珀酸对AA肉鸡生产性能和肠道健康的影响。选用1日龄健康AA肉鸡240羽,根据体重随机分为4组,每组5个重复,每个重复12羽。对照组饲喂基础日粮,抗生素组在基础日粮中添加15 mg/kg维吉尼亚霉素,低剂量和高剂量琥珀酸组分别在基础日粮中添加1 g/kg和2 g/kg琥珀酸。试验期为42 d(1~21 d和22~42 d)。结果表明:与对照组相比,高剂量琥珀酸能够提高肉鸡全净膛率(P<0.05);与抗生素组相比,低剂量琥珀酸能够提高肉鸡血清尿酸和尿素氮水平(P<0.05);日粮中添加琥珀酸对肉鸡肠道形态结构和盲肠微生物组成影响较小,但与对照组相比,添加低剂量和高剂量琥珀酸具有下调肠道炎症因子基因IL-4 mRNA表达的趋势(P=0.0992和P=0.0728),添加高剂量琥珀酸还上调了IFN-γ mRNA的表达(P<0.05),提示日粮中添加琥珀酸有利于缓解肉鸡肠道炎症,调节免疫力。由此可见,日粮中添加高剂量(2 g/kg)琥珀酸能够促进肉鸡生长发育、缓解肠道炎症、调节免疫力,而添加低剂量(1 g/kg)琥珀酸则可以改善机体氨氮代谢水平。

Effect of Sc on Al_(3)Fe phase and mechanical properties of as-cast AA5052 aluminum alloy

The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous studies have demonstrated that the addition of Sc to aluminum alloys can improve both the microstructure and properties of the alloys.In this study,the effect of Sc on the Fe-rich phase and properties of the AA5052 aluminum alloy was studied by adding 0%,0.05%,0.2%,and 0.3%Sc.The results show that with the increase of Sc,the coarse needle-like Fe-rich phase gradually transforms into Chinese-script and then nearly spherical particles,reduce the size of Fe-rich phase,and refine the grain with increase of high angle grain boundaries(HAGBs).These microstructure changes enhance the strength of the AA5052 alloy through Sc addition.The ductility of the alloy is obviously improved because the addition of a lower amount of Sc changes the morphology of Fe-rich phase from needle-like into a Chinese-script,and it is subsequently reduced as a result of significant increase in HAGBs with increasing Sc content.

AA2195-AZ31B搅拌摩擦焊温度与残余应力场的数值模拟

针对AA2195铝锂合金和AZ31B镁合金,基于耦合欧拉拉格朗日(coupled eulerian-lagrangian,CEL)方法,结合有限元分析软件Abaqus,建立了搅拌摩擦焊对接过程的有限元模型。同时,对焊接过程中的动态温度场及焊后残余应力场的分布进行了研究。结果表明:焊缝区域应力以纵向应力为主,最大残余应力在AA2195铝锂合金侧。垂直于焊缝的截面纵向应力呈“M”形分布,最大值约为220 MPa,双峰之间存在倒“V”形。焊接过程中温度变化趋势与应力循环曲线负相关。此外,针对2 mm厚的AA2195铝锂合金和AZ31B镁合金板材进行了搅拌摩擦焊试验,用盲孔法对焊后残余应力进行测试,验证了模型的准确性。

ICP-OES与AAS测定门窗幕墙用型材表面涂层中可溶性重金属Pb和Cd

分别采用原子吸收分光光度法(AAS)和电感耦合等离子体发射光谱法(ICP-OES)对门窗幕墙用型材表面涂层中可溶性重金属Pb、Cd的含量进行测定,对方法的检出限、测定下限、准确度和精密度进行分析。结果表明,ICP-OES相较于AAS在准确度、检出限、测定下限和检测效率上有显著优势。ICP-OES在测定铝合金建筑型材表面涂层中可溶性重金属Pb、Cd含量上应用前景广阔。

复方氨基酸注射液(18AA)中组胺类物质检查和降压物质检查比较

目的:探讨复方氨基酸注射液(18AA)安全检查中,以组胺类物质检查法替代降压物质检查法的可能性。方法:探讨按照《中国药典》2020年版四部中的降压物质和组胺类物质的规定,分别对3批复方氨基酸注射液(18AA)进行降压物质检查和组胺类物质检查,比较两种方法结果的异同。结果:根据药典标准判定,3批复方氨基酸注射液(18AA)方法适用性通过且降压物质检查和组胺类物质检查结果均符合规定。结论:复方氨基酸注射液(18AA)的组胺类物质检查法可以作为降压物质检查法的补充,组胺类物质检查法的灵敏性有待商确。

Ywhab通过靶向Hsp90aa1抑制小鼠B细胞淋巴瘤38B9细胞生长

目的:研究Ywhab在小鼠B细胞淋巴瘤发生发展中的作用,并探讨其可能的分子机制。方法:使用生物信息学分析Ywhab与弥漫性大B细胞淋巴瘤(DLBCL)的相关性。在小鼠B细胞淋巴瘤38B9细胞中感染逆转录病毒构建Ywhab基因过表达细胞系,并采用RT-qPCR和Western blot验证Ywhab的mRNA及蛋白(14-3-3β)水平;通过细胞计数法、CCK-8法和小鼠皮下成瘤实验检测Ywhab过表达对38B9细胞在体内外生长的影响;RT-qPCR和Western blot检测细胞凋亡相关蛋白的表达;应用蛋白质免疫共沉淀联合蛋白质谱(CoIP-MS)筛选与14-3-3β特异性结合的蛋白并采用Western blot及分子对接分析进行验证。结果:Ywhab基因在DLBCL中低表达,其低表达预示DLBCL患者的临床预后较差。与正常小鼠骨髓B细胞相比,Ywhab在38B9细胞中低表达。Ywhab过表达能在体内外诱导38B9细胞凋亡,促进凋亡蛋白Puma、Noxa和Bax的mRNA及蛋白表达,抑制抗凋亡蛋白Bcl2的mRNA及蛋白表达(P<0.05)。14-3-3β蛋白能特异性结合Hsp90aa1蛋白并抑制其表达,从而促进38B9细胞凋亡。结论:Ywhab能够显著诱导小鼠B细胞淋巴瘤38B9细胞凋亡,其机制可能是通过靶向抑制Hsp90aa1蛋白表达来实现的。

2.25Cr1Mo0.25V耐热钢与304不锈钢AA-TIG焊接接头组织及性能研究

采用电弧辅助活性AA-TIG焊对2.25Cr1Mo0.25V耐热钢和304不锈钢管进行异种钢材焊接,并对其焊接接头的组织、硬度及力学性能进行分析。结果表明,使用AA-TIG焊能够一次性焊透2.25Cr1Mo0.25V耐热钢和304不锈钢,得到成形良好的焊接接头。焊缝处无裂纹等焊接缺陷,焊缝处各元素在焊缝水平方向分布均匀。在靠近两侧母材的焊缝区,Cr、Fe、Ni元素有一定的梯度,但无明显偏聚。焊接接头两边的母材区硬度值较低,在焊缝区域硬度达到最大,焊缝区域的硬度波动范围在400~489 HV之间,最终拉伸试样都断在304母材上,得到的平均拉伸强度为406 MPa,最大的抗拉强度为542 MPa。

混凝沉淀-气浮-ABR-AA/O-MBR工艺处理垃圾中转站渗滤液的试验研究

垃圾中转站运行过程中产生的垃圾渗滤液含有大量的悬浮固体、油脂、有机物、盐分、氮类等污染物,其水质复杂且波动性大,易造成环境污染。针对浙江省某垃圾中转站渗滤液的水量和水质特点,采用混凝沉淀-气浮-ABR-AA/O-MBR工艺进行试验研究。其中,混凝沉淀-气浮物化处理单元能有效去除渗滤液中的悬浮固体和油脂等,而ABR-AA/O生物处理单元则能有效去除有机物、氨氮和总氮等。试验结果表明:进水中的COD_(Cr)、NH_(4)^(+)-N、TN和SS浓度分别为15130~20540、278.0~413.0、289.0~437.0和4330~6317 mg/L,出水中的COD_(Cr)、NH_(4)^(+)-N、TN和SS浓度分别为134~313、0.4~0.9、46.4~65.1和8~14 mg/L,平均去除率分别为98.72%、99.81%、84.91%和99.79%,满足《污水排入城镇下水道水质标准》(GB/T 31962—2015)的要求。综合来看,此工艺具有良好的技术适应性和产业化前景。