Background:Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is molecularly heterogeneous and influenced by the bone marrow microenvironment. Mesenchymal stromal cells (MSCs) provide critical niche signals, yet their transcriptomic remodeling in B-ALL is poorly defined. This study aims to define a compact gene signature that complements blast-centric diagnostics. Methods:We analyzed GSE101425 (GPL570) MSC microarrays (rather than leukemic blasts) from pediatric B-ALL at diagnosis (day 0, n=35), remission (n=29), relapse (n=6), and healthy donors (n=16). Differential expression (day 0 vs. healthy), Random Forest feature ranking, consensus clustering, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses were performed. Within-cohort discrimination used 5-fold cross-validated logistic regression with bootstrapped area under the receiver operating characteristic curve (AUC) confidence intervals (CIs) (CCN4 mapped to WISP1 on GPL570). Public single-cell RNA sequencing (scRNA-seq) data provided cellular context. Peripheral blood real-time quantitative PCR (RT-qPCR) served as an exploratory assessment of systemic expression, not MSC validation. Results:We identified 78 differentially expressed genes (DEGs) in B-ALL-associated MSCs. A four-gene MSC signature [Dickkopf WNT Signaling Pathway Inhibitor 1 (DKK1), Regulator of G Protein Signaling 2 (RGS2), Cellular Communication Network Factor 4/WNT1-Inducible Signaling Pathway Protein 1 (CCN4/WISP1), Lysozyme (LYZ)] distinguished active B-ALL MSCs from healthy MSCs with cross-validated AUC 0.883 (95% CI: 0.783-0.966) and separated samples into two transcriptional states with distinct pathway enrichment, including extracellular matrix and immune-related programs. Single-cell data localized RGS2 and LYZ to immune compartments, whereas DKK1 and CCN4/WISP1 were low, supporting stromal specificity. Peripheral blood RT-qPCR showed decreased RGS2 and LYZ, whereas CCN4 showed a nonsignificant upward trend (P=0.053), underscoring compartment-dependent patterns. Conclusions:These data delineate transcriptional remodeling of bone marrow MSCs in pediatric B-ALL and nominate a four-gene MSC-associated signature. By centering on stromal MSC transcriptomes rather than leukemic blasts, we target a complementary microenvironmental layer of B-ALL biology that is underrepresented in blast-centric transcriptomics. The findings are hypothesis-generating and require independent MSC cohorts and functional validation.

Moyamoya disease is a rare, chronic cerebrovascular disorder characterized by progressive stenosis or occlusion of the terminal portions of the internal carotid arteries and the subsequent development of abnormal compensatory vascular networks. It represents a significant cause of intracranial arteriopathy and is a major etiology of stroke and transient ischemic attack in pediatric populations. We present the case of a 9-year-old boy with confirmed diagnosis of B-cell acute lymphoblastic leukemia (B-ALL), in whom brain MRI findings were suggestive of Moyamoya disease. This report underscores the rarity of the co-occurrence of B-ALL and Moyamoya disease and highlights the importance of early recognition and timely intervention during chemotherapy to reduce the risk of neurological complications. Our findings may offer valuable insights for the chemotherapeutic management of ALL patients with coexisting Moyamoya disease.

Ethnopharmacological relevance Chronic immune thrombocytopenia (CITP) seriously affects the patients’ quality of life. In the real world, a traditional Chinese medicine, Huaiqihuang Granule (HQH) shows certain value in ITP treatment.It primarily comprises Huai’er(Trametes robiniophia Murr), Gouqizi(Lycium chinense Mill), Huangjing(Polygonatum sibiricum F. Delaroche). Aim of the study This study aims to investigate the clinical efficacy and safety of HQH in children with CITP. Materials and Methods A multi-centre, randomized, double-blind, placebo- controlled clinical trial was conducted among 216 children with CITP from June 27, 2017 to October 14, 2023, at 13 hospitals in China. Patients were followed up for 96 weeks. Patients with CITP were treated with HQH or with matching placebo in a randomized, double-blind, 24-week treatment period. Patients who received placebo and completed 24 weeks of treatment switched to receive HQH, and patients treated with HQH in the double-blind period continued HQH during the following open-label 24-week treatment. Results HQH was superior to placebo in decreasing the bleeding grade and achieving a platelet response. The total clinical effectiveness rate of HQH group (71.74% in 24-week) was higher than that of the placebo group (45.65% in 24-week, p=0.0013). The result was similarly seen when the data of patients with rescue treatment was analyzed as ineffectiveness or excluded. AEs and serious AE was comparable between the two groups. The severe AEs included thrombocytopenia (6.9%), respiratory tract infection (5.1%) and hemorrhagic episodes (2.8%). Conclusions In CITP children, HQH can improve the clinical effectiveness especially the degree of bleeding, and shows good safety even with long-term treatment.

Recently protein binders have emerged as a promising substitute for antibodies due to their high specificity and low cost. Herein, we demonstrate an electrochemical biosensor chip through the electronic labelling strategy using lead sulfide (PbS) colloidal quantum dots (CQDs) and the unnatural SARS-CoV-2 spike miniprotein receptor LCB. The unnatural receptor can be utilized as a molecular probe for the construction of CQD-based electrochemical biosensor chips, through which the specific binding of LCB and the spike protein is transduced to sensor electrical signals. The biosensor exhibits a good linear response in the concentration range of 10 pg mL-1 to 1 μg mL-1 (13.94 fM to 1.394 nM) with the limit of detection (LOD) being 3.31 pg mL-1 (4.607 fM for the three-electrode system) and 9.58 fg mL-1 (0.013 fM for the HEMT device). Due to the high sensitivity of the electrochemical biosensor, it was also used to study the binding kinetics between the unnatural receptor LCB and spike protein, which has achieved comparable results as those obtained with commercial equipment. To the best of our knowledge, this is the first example of using a computationally designed miniprotein receptor based on electrochemical methods, and it is the first kinetic assay performed with an electrochemical assay alone. The miniprotein receptor electrochemical biosensor based on QDs is desirable for fabricating high-throughput, large-area, wafer-scale biochips.

Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignant tumor in children. This study aimed to investigate the lymphocyte subsets, their activities and dynamic changes during and after chemotherapy in children wiht B-ALL. Methods: Peripheral blood samples were prospectively and cross-sectional collected from B-ALL children at different treatment time points (50 cases at initial diagnosis, 40 cases after induction, 20 cases at the beginning of maintenance, 15 cases at 61 weeks, the middle of maintenance, 20 cases at the end of treatment, 18 cases at 5-year follow-up) and healthy control children. T, B and NK lymphocyte subsets, immunophenotypes and functions were detected by flow cytometry. Results: Compared with healthy controls, T cells in patients newly diagnosed with B-ALL were in a state of inhibition, senescence and exhaustion. The percentages of CD4+, CD4/CD8, γδ T, CD4+Tnaive as well as CD8+Tnaive were significantly decreased (P < 0.05). The percentages of CD8+, Tregs, CD4+Tcm, CD8+Tem, CD4+PD-1, CD4+TIM-3, CD8+PD-1 and CD8+TIM-3 were significantly increased (P < 0.05). The levels of IFN-γ, IL-4 and IL-2 were significantly lower. NK and NKT cells in B-ALL children were in a state of inhibition, which mainly showed that the percentage of NK and NKT was significantly decreased, and the activator receptor NKP46 and NKG2D were significantly decreased (P < 0.05). After induction therapy, the percentage of B cells decreased significantly (P=0.000), and T cells and NK cells had a partial recovery (P < 0.05). When entering to maintenance therapy, T, B, NK cell percentage and T cell function of patients were the most severely impaired, and then gradually recovered. Till to the end of treatment, the function of lymphocytewas inhibited. At 5 years follow-up, the counts and functions of B and NK cells recovered, but that of T cells did not recover completely. Conclusions: The absolute counts and functions of T cells and NK cells, which were significantly lower in children with B-ALL, gradually recovered after chemotherapy. Detecting the counts and functions of peripheral blood lymphocytes is important for identifying new prognostic markers of ALL, guiding to prevent infection and administering effective immunotherapy.

The efficacy and safety of Huaiqihuang Granules in the treatment of childhood chronic primary immune thrombocytopenia: a multicentre, randomized, double-blind, placebo-controlled clinical study * Correspondence: Fen Zhou, daisy_may@163.com Runming Jin, jinrunm@qq.com Abstract Background: Chronic immune thrombocytopenia (CITP) is a hemorrhagic disease that seriously affects the quality of life of children and their families. Huaiqihuang Granules, a traditional Chinese medicine, has certain value in the treatment of ITP patients in the preliminary clinical findings. To investigate the efficacy and safety of Huaiqihuang Granules in children with CITP, we conducted a multicenter, randomized, double-blind, placebo-controlled study. Methods: Patients with CITP were treated with Huaiqihuang Granules or with matching placebo in a randomized, double-blind, 24-week treatment period. Patients who received placebo and completed 24 weeks of treatment switched to receive Huaiqihuang Granules, and patients treated with Huaiqihuang Granules in the double-blind period continued Huaiqihuang Granules during the following open-label 24-week treatment.The patients were followed up for 96 weeks. Clinical effective (defined as those achieving a platelet count of≥30×109/L and at least twofold more than the basal platelet count, or the degree of bleeding decreased by one or more grade) was evaluated. Results: Huaiqihuang Granules was superior to placebo in achieving a platelet response and in reducing the bleeding risk. The clinical effective rate of Huaiqihuang Granules group (71.74% in 24-week) was higher than that of the Placebo group (45.65% in 24-week, p=0.0013). The most common severe adverse events were respiratory tract infection (7.8%) and immune thrombocytopenic purpura (6.9%) . Conclusions: In CITP children, Huaiqihuang granules can improve the clinical effectiveness especially the degree of bleeding, and shows good safety in long-term treatment. Keywords: Chronic immune thrombocytopenia, Huaiqihuang Granules, efficacy; safety

目的:基于德尔菲法构建恶性梗阻性黄疸经皮肝穿刺胆管引流术(PTCD)带管病人以家庭为中心的干预方案,为今后恶性梗阻性黄疸PTCD带管病人的延续性护理管理模式提供实践参考.方法:2020年9月通过文献分析法形成恶性梗阻性黄疸PTCD带管病人以家庭为中心干预方案初稿,选取19名专家进行两轮德尔菲专家咨询,修订形成最终的干预方案.结果:两轮专家权威系数分别为0.824,0.874,均>0.700;第1轮专家咨询各条目重要性得分均数在2.142～5.000,第2轮咨询各条目重要性得分均数在3.686～4.905,均>3.500,且第2轮专家咨询中所有条目变异系数CV均＜0.25;第1轮专家咨询肯德尔协调系数(W值)为0.524,第2轮专家咨询W值为0.535,两轮专家咨询W值的显著性检验均P＜0.01.最终构建的以家庭为中心的干预方案包括5个要素、5个时间节点、17个条目.结论:恶性梗阻性黄疸PTCD带管病人以家庭为中心的干预方案是在文献回顾、德尔菲专家咨询的基础上制定的,该方案的制定过程具有一定的科学性及严谨性,为恶性梗阻性黄疸PTCD带管病人的延续性护理模式提供了实践参考.

目的 了解护理本科生对护理专业课程思政知信行现状,并探讨其影响因素,为本科护理专业课程思政教学提供参考.方法 采用 自行编制的护理专业课程思政知信行问卷,对294名护理本科生进行调查.结果 护理本科生对护理专业课程思政知信行总分为(91.10±10.40)分,其中知识、态度、行为得分分别为(23.71±3.17)、(28.81±4.02)和(38.57±5.06)分.多元线性回归分析显示,对护理专业的喜爱程度、参与相关课程思政教学情况及高校组织思政相关活动情况是护理本科生课程思政知信行的影响因素(均P＜0.05).结论 护理本科生对护理专业课程思政的知信行处于中等偏上水平,教学过程中应重点关注非 自主选择护理专业、对护理专业喜爱程度低的护理本科生,调动护理本科生参与课程思政积极性,加强并优化课程思政建设的力度和形式,从而进一步提高护理本科生对护理专业课程思政的知信行水平.

Abstract Background Infection is the most common adverse event of acute lymphoblastic leukemia (ALL) treatment and is also one of the main causes of death. Methods To investigate the clinical characteristics and risk factors of severe infections during the maintenance phase of ALL treatment, we conducted a retrospective study. Results A total of 181 children were eligible and 46 patients (25.4%) suffered from 51 events of severe infection, most of which occurred in the first half year of the maintenance phase (52.9%). The most common infection was pulmonary infection (86.3%) followed by bloodstream infection (19.6%). The main symptoms of ALL patients with pulmonary infection were fever, cough, and shortness of breath. The main manifestations of computer tomography (CT) were ground glass shadow (56.8%), consolidation shadow (27.3%), and streak shadow (25%). Multivariate binary logistic regression analysis showed that agranulocytosis, agranulocytosis ≥7 days, anemia, and low globulin level were independent risk factors for severe infection during the maintenance phase (all p < 0.05). Conclusions Taken together, blood routine examinations and protein levels should be monitored regularly for ALL patients in the maintenance phase, especially in the first 6 months. For ALL patients with risk factors, preventive anti‐infective or supportive therapies can be given as appropriate to reduce the occurrence of severe infections.

Hypothyroidism as a long-term complication in cancer survivors has been an issue, but few studies have focused on changes in thyroid hormone levels during chemotherapy for leukaemia. This retrospective study was conducted to assess the characteristics of children with acute lymphoblastic leukaemia (ALL) and hypothyroidism during induction chemotherapy and to investigate the prognostic value of hypothyroidism in ALL. Patients with a detailed thyroid hormone profile at ALL diagnosis were enrolled. Hypothyroidism was defined as low serum levels of free tetraiodothyronine (FT4) and/or free triiodothyronine (FT3). The Kaplan-Meier method was used to create survival curves, and multivariate Cox regression analysis was used to screen prognostic factors associated with progression-free survival (PFS) and overall survival (OS). There were 276 children eligible for the study, and 184 patients (66.67%) were diagnosed with hypothyroidism, including 90 cases (48.91%) with functional central hypothyroidism and 82 cases (44.57%) with low T3 syndrome. Hypothyroidism was correlated with the dosages of L-Asparaginase (L-Asp) (P = .004) and glucocorticoids (P = .010), central nervous system (CNS) status (P = .012), number of severe infections (grade 3, 4 or 5) (P = .026) and serum albumin level (P = .032). Hypothyroidism was an independent prognostic factor for PFS in ALL children (P = .024, 95% CI: 1.1-4.1). We conclude that hypothyroidism is commonly present in ALL children during induction remission, which is related to chemotherapy drugs and severe infections. Hypothyroidism was a predictor of poor prognosis in childhood ALL.

目的 探讨高危风险预警模式结合康复教育路径在胰腺癌患者围手术期护理中的应用效果.方法 采用便利抽样法选取本院2019年6月—2021年8月收治的98例胰腺癌患者为研究对象,依据随机数字表法将其分为参照组和研究组,每组各49例.参照组实施常规围手术期护理,研究组在参照组的基础上实施高危风险预警模式结合康复教育路径.比较两组患者的疾病认知情况、术后康复情况、并发症发生情况及生命质量.结果 研究组的疾病认知评分均高于参照组(P<0.05);研究组术后康复情况显著优于参照组(P<0.05),并发症发生率显著低于参照组(P<0.05),生命质量评分显著高于参照组,差异有统计学意义(P<0.05).结论 实施高危风险预警模式结合康复教育路径能有效提升胰腺癌患者的疾病认知程度,降低围手术期不良事件与并发症的发生风险,促进患者术后康复,改善其生命质量,值得临床应用与推广.

Objective To investigate current status of the public′s perception of nurse role and nursing profession, and to provide re-ferences for the development of nursing profession.Methods We conducted an online survey with a self-designed questionnaire.The contents of the questionnaire included respondents′ demographics, their perception on nurse role and cognition of nursing profession.Results A total of 942 valid questionnaires were collected.The public′s first impression of nurses was positive.The highest expectations of the general public for "excellent nurses" were "good attitude"（91.22%） and "responsible"（91.22%）, while the highest expectation of nurses for "being excellent nurses" was "professional knowledge and solid skills"（94.27%）.The majority of the public agreed that there was a shortage of nurses, with 60.82% of the general public and 29.30% of nurses saying "will/may recommend friends and relatives to the nursing profession".Conclusion In general, the public had a positive evaluation on the role of nurses and nursing profession, but they don′t have a full picture of image of nurses.Nursing staff and nursing managers should take active actions to continuously improve the image of nurses, so as to improve the public′s understanding and support of nursing profession.

For patients with refractory breast cancer (BC), integrative immunotherapies are emerging as a critical component of treatment. However, many patients remain unresponsive to treatment or relapse after a period. Different cells and mediators in the tumor microenvironment (TME) play important roles in the progression of BC, and cancer stem cells (CSCs) are deemed the main cause of relapse. Their characteristics depend on their interactions with their microenvironment as well as on the inducing factors and elements in this environment. Strategies to modulate the immune system in the TME of BC that are aimed at reversing the suppressive networks within it and eradicating residual CSCs are, thus, essential for improving the current therapeutic efficacy of BC. This review focuses on the development of immunoresistance in BCs and discusses the strategies that can modulate the immune system and target breast CSCs directly to treat BC including immunotherapy with immune checkpoint blockades.

目的 基于泰勒模式构建本科外科护理学课程思政教学指标体系,为本科外科护理思政教育建设提供参考.方法 通过文献分析初步构建本科外科护理学课程思政教学指标体系,于2021年11月—2022年1月选取12名专家进行2轮函询.对各级指标进行筛选、修改和完善,确立本科外科护理学课程思政教学指标体系.结果 2轮专家函询问卷有效回收率均为100％,专家权威系数均为0.87;2轮函询的肯德尔和谐系数分别为0.193、0.411(P＜0.01).最终构建的本科外科护理学课程思政教学指标包括4项一级指标(教育目标、教育内容、教育方法、教育评价)、9项二级指标、40项三级指标.结论 本科外科护理学课程思政教学指标体系具有较好的科学性与可靠性,为本科外科护理思政教育建设提供参考.

目的:探讨"互联网+护理"模式在老年恶性梗阻性黄疸病人中的应用效果.方法:2020年1月—2021年12月选取88例进行经皮肝穿刺胆道引流术(PTBD)治疗的老年恶性梗阻性黄疸病人为研究对象,利用"随机单双号"方式将其分为对照组与试验组各44例.对照组给予围术期常规人文关怀+加强健康教育,并联合延续护理,试验组基于对照组实施"互联网+护理"模式,比较两组病人自我护理能力、胃管留置时间、疼痛、围术期内并发症发生情况、焦虑情况以及对护理工作的满意度.结果:试验组病人干预后自我护理、自我责任感、自我概念、健康知识水平各维度评分均高于对照组(P<0.05);试验组病人胃管留置时间短于对照组(P<0.05);试验组中重度疼痛病人占比明显低于对照组(P<0.05);试验组病人围术期并发症发生率低于对照组(P<0.05);试验组病人焦虑评分低于对照组(P<0.05);试验组病人护理工作满意度明显优于对照组(P<0.05).结论:实施"互联网+护理"模式能够有效提升老年恶性梗阻性黄疸病人自我护理能力,缩短胃管留置时间,减轻疼痛感受与焦虑感,降低并发症发生率,同时提高了病人护理工作满意度.

Rapid screening of microorganisms with good saline-alkali tolerance is of great significance for the improvement of saline-alkali land. In this study, a novel electrochemical method was developed for the rapid screening of saline-alkali-tolerant bacteria using a hydrogel/gold nanoparticles-modified screen-printed electrode. Monitoring bacterial growth using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) yielded a new method to measure saline-alkali sensitivity. The strains were deposited on agarose hydrogel-AuNPs composite-modified electrodes with saline-alkali treatment control at a concentration of 50 mM. The electrochemical-derived growth curve of each bacterial strain was established to monitor the effect of saline-alkaline conditions on bacterial growth. The results showed that E. coli could grow on the hydrogel-AuNPs composite-modified electrodes without saline and alkali, while the growth of E. coli was inhibited after adding saline and alkali to the modified electrodes. In contrast, Paenibacillus lautus (HC_A) and Lysinibacillus fusiformis (HC_B) were able to grow on electrodes containing saline-alkali hydrogel-AuNPs composite modification. This fast growth curves of the strains derived from electrochemical analysis indicate that the possible time for salinity sensitivity results is <45 min. Compared to the traditional bacterial culture method lasting at least 1-2 days, this method has the clear advantages of rapidity, high efficiency, and low cost.

Salinization is a severe problem in cultivated soil worldwide. Bioremediation has become an emerging method for saline-alkali soil remediation due to its advantages of low cost, high efficiency, and environmental friendliness. Saline-alkali-tolerant microorganisms are an important component of bioremediation. Rapid screening of microorganisms with good saline-alkali tolerance is of great significance for the improvement of saline-alkali land and the development of new bacterial agents. In this study, a novel electrochemical method was developed for the rapid screening of saline-alkali-tolerant bacteria, using a low-cost, commercially available screen-printed electrode. The electrodes were modified with agarose-based hydrogels or hydrogel/gold nanoparticles (AuNPs) deposits. Monitoring bacterial growth using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) yielded a new method to measure saline-alkali sensitivity. The strains were deposited on agarose hydrogel-AuNPs composite-modified electrodes with saline-alkali treatment. The electrochemical-derived growth curve of each bacterial strain was established to monitor the effect of saline-alkaline on bacterial growth. The results showed that E. coli could grow on the hydrogel-AuNPs composite-modified electrodes without saline and alkali, while the growth of E. coli was inhibited after adding saline and alkali to the modified electrodes. In contrast, Paenibacillus lautus (HC_A) and Lysinibacillus fusiformis (HC_B) were able to grow on electrodes containing the saline-alkali hydrogel-AuNPs composite modification. This fast growth curve of the strain derived from electrochemical analysis indicates that the possible time for salinity sensitivity results is <45 min. Compared with the traditional bacterial culture method lasting at least 1-2 days, this method has the clear advantages of rapidity, high efficiency, and low cost.

The commensal microbiome refers to a large spectrum of microorganisms which mainly consists of viruses and bacteria, as well as some other components such as protozoa and fungi. Epstein-Barr virus (EBV) is considered as a common component of the human commensal microbiome due to its spread worldwide in about 95% of the adult population. As the first oncogenic virus recognized in human, numerous studies have reported the involvement of other components of the commensal microbiome in the increasing incidence of EBV-driven cancers. Additionally, recent advances have also defined the involvement of host-microbiota interactions in the regulation of the host immune system in EBV-driven cancers as well as other circumstances. The regulation of the host immune system by the commensal microbiome coinfects with EBV could be the implications for how we understand the persistence and reactivation of EBV, as well as the progression of EBV-associated cancers, since majority of the EBV persist as asymptomatic carrier. In this review, we attempt to summarize the possible mechanisms for EBV latency, reactivation, and EBV-driven tumorigenesis, as well as casting light on the role of other components of the microbiome in EBV infection and reactivation. Besides, whether novel microbiome targeting strategies could be applied for curing of EBV-driven cancer is discussed as well.

总结1例出血坏死型胰腺炎伴重度腹泻致失禁性皮炎病人的伤口护理经验,护理要点:针对性采取控制全身性疾病因素感染的措施,制定失禁性皮炎伤口各级的护理方案;积极预防及处理重度腹泻;保持皮肤黏膜完整性,加强全身功能锻炼,增加机体免疫力,恢复肠道正常菌群,提高肠内营养耐受性,促进疾病康复.