M2-like macrophages play a critical role in breast cancer progression. Although JMJD3 is reported to play a significant role in M2-like macrophage polarization, its precise mechanism remains unclear. By using PMA, IL-4, and IL-13, we successfully induced THP-1 cells into M2-like macrophages, which subsequently promoted breast cancer cell proliferation and inhibited apoptosis, accompanied by increased JMJD3 expression. We demonstrated that JMJD3 enhances M2-like macrophage polarization: knockdown of JMJD3 decreased the M2-like macrophage gene expression, while overexpression of JMJD3 produced the opposite effects. Furthermore, JMJD3 promoted M2-like macrophage polarization through the STAT6/IRF4 axis. Knockdown of JMJD3 abrogated IL-4/IL-13 induced IRF4 expression, while overexpression of JMJD3 upregulated IRF4 expression. Inhibition of STAT6 downregulated the expression of JMJD3, IRF4, and M2-like macrophage marker genes. Additionally, inhibiting JMJD3 and STAT6 in macrophages increased cell apoptosis and decreased cell viability in breast cancer cells, while JMJD3 overexpression exhibited pro-tumor activity. In conclusion, our findings highlight the role of JMJD3 in regulating M2-like macrophage polarization and its impact on breast cancer development through the STAT6/IRF4 axis.
OBJECTIVE:To elucidate the genetic aetiology of basal cell nevus syndrome (BCNS) within a Chinese cohort featuring an affected family. METHODS:The patient's and their parents' peripheral venous blood was collected for high-throughput exon sequencing. Tools such as Mutation Taster2 and SIFT were used to predict mutation harmfulness and obtain the most suspected pathogenic mutation. GeneMANIA was employed to construct the protein interaction network between the gene and Hedgehog pathway. SWISS-MODEL was used to simulate the bioinformatics structure changes of the mutant gene and HDOCK was utilised to simulate molecular docking. Finally, the function of this gene mutation was verified by q-PCR. RESULTS:A novel pathogenic mutation of PTCHD3 was identified. CCDC57 in the Hedgehog pathway was found to interact with PTCHD3 through GeneMANIA. SWISS-MODEL predicted that PTCHD3 mutation would lead to changes in the 3D structure of the protein. HDOCK showed that the binding between PTCHD3 and CCDC57 was significantly reduced. The mutation of PTCHD3 may result in decreased binding ability of PTCHD3 to CCDC57, activate the Hedgehog pathway and lead to the occurrence of the disease. The diagnosis and treatment pathway for clinical discovery of OKC was provided. CONCLUSION:A novel pathogenic mutation of PTCHD3 was identified in Chinese BCNS patients. PTCHD3 may play a role in various biological processes mediated by the Hedgehog signalling pathway and is expected to be a new potential therapeutic target.
Organoids become powerful platforms for modeling cancer biology but poorly preserve stemness due to inadequate biophysical cues. Cancer stem cells (CSCs), crucial for tumor growth, are rare and lose stemness under conventional in vitro conditions, limiting drug screening. While chemical and genetic stemness regulators are identified, the role of spatial matrix mechanics remains unclear and largely absent from current organoid architectures. Here, we demonstrate that stemness depends not on stiffness alone but on 3D spatial stiffness differentials across distinct microenvironmental regions. Single-cell clustering and spatial localization analyses reveal that CSCs localize at tumor invasive fronts. In vitro mechanobiological studies further identify that Janus stiffness sustains stemness by altering E-cadherin/β-catenin interactions, triggering nuclear β-catenin and stemness programs. Using this insight, we print Janus microsphere sandwiches using a coaxial co-flow capillary microfluidic device, confining cells between mechanically distinct hydrogel layers to encode cellular-scale stiffness gradients, a feature unattainable in conventional single-layer microspheres or bulk-embedded organoids. This architecture mimics CSC spatial distribution in oral squamous cell carcinoma, maintaining stemness and enabling robust drug screening. By transforming a previously underrepresented mechanobiological mechanism into an engineerable organoid, we create new biomimetic tumor organoid where spatially programmed mechanics, not just biochemistry, governs stemness and therapeutic relevance.
OBJECTIVES:This study aimed to systematically compare the efficacy and resorption of in-situ and ex-situ bone onlay grafting in reconstructing horizontal alveolar ridge defects of anterior teeth. METHODS:One-hundred and twenty five patients receiving autogenous bone onlay grafts in the anterior tooth region were included in this study, which comprised 55 patients with 66 implants receiving in-situ bone grafts (in-situ group) and 70 patients with 77 implants receiving ex-situ bone grafts (ex-situ group). All patients were examined by CBCT scanning before bone augmentation (T0), immediately after bone augmentation (T1), at 5-8 months after bone augmentation (T2), immediately after implant placement (T3), and 5-8 months after implant placement (T4). Horizontal bone width (HBW) and bone volume (BV) were measured at different postoperative time points after automated image registration of consecutive CBCT imaging. RESULTS:The resorption rate of HBW from T1 to T2 in the in-situ group (23.84% ± 17.07%) was significantly lower than that in the ex-situ group (38.77% ± 19.94%) (p < 0.0001). However, from T3 to T4, no significant difference was observed between the two groups. Additionally, from T1 to T2, there were significant differences in the resorption rate of BV between the in-situ group (20.03% ± 16.14%) and the ex-situ group (28.20% ± 17.58%) (p < 0.05). In contrast, no significant differences between the two groups from T3 to T4 were noted. CONCLUSIONS:Both in-situ and ex-situ onlay graftings showed a satisfactory outcome in bone augmentation, yet in-situ bone graft had more bone augmentation and better stability than ex-situ bone graft.
The curvatures within the human body have essential functions, but their fabrication remains relatively unexplored. We re-emphasize the importance of curvatures in native biological tissues, present technologies to fabricate biomimetic curvatures, and discuss the challenges of integrating curvatures into biomanufacturing. Finally, we recommend how to incorporate curvatures into engineered tissues.
AIM:This study aimed to explore the experiences of haematology nurses while caring for patients undergoing haematopoietic stem cell transplantation. DESIGN:A qualitative descriptive study was conducted. METHODS:We conducted semi-structured interviews with 18 haematology nurses in six hospitals between May 2022 and December 2023. The data were analysed using traditional content analysis. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist guided this report. The data were saturated in the 16th interview, and two more were conducted to confirm data saturation. RESULTS:Through analysis, four themes and eleven sub-themes regarding the caring experiences of haematopoietic stem cell transplantation patients have emerged: challenges of isolated spaces, including the 'claustrophobic' feeling in isolated environments, segregation of communication, and pressure to independently assess and manage patient care; moral distress from treatment decisions, encompassing struggles in weighing haematopoietic stem cell transplantation pros and cons during patient communication, providing 'insincere' encouragement to patients, and doubting the meaning of persistence; reciprocal dedication in nurse-patient relationships, characterised by nurses' emotional investment in care and patients' positive feedback as motivation; and increased sense of professional value, demonstrated through increased confidence in caregiving, enhanced self-care ability, and achievement of job fulfilment. CONCLUSIONS:This study explores the real and intuitive experiences of haematology nurses caring for haematopoietic stem cell transplantation patients in China, enhancing our understanding of the care process. It revealed haematology nurses' challenges and positive experiences in caring for haematopoietic stem cell transplantation patients. IMPACT:This study provides evidence to optimise the haematopoietic stem cell transplantation nursing process and develop targeted support systems, which are crucial for enhancing nurses' sense of professional value and ensuring their well-being. PATIENT OR PUBLIC CONTRIBUTION:This paper benefited from the contributions of 18 haematology nurses, who shared their valuable experiences and emotions.
Abstract Background Primary failure of eruption (PFE) is a rare disorder characterized by a posterior open bite. While mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been demonstrated to cause PFE, the underlying mechanisms remain largely unknown. Methods Whole exome sequencing was conducted to identify PTH1R variants in a PFE family. MG63 cells that stably expressed the corresponding mutant PTH1R were established using lentiviruses. Next, osteogenesis was assessed by measuring cell alkaline phosphatase activity, conducting alizarin red staining, and evaluating osteoblast-specific gene expression. Then, computational analysis of binding affinity and RNA sequencing were carried out. Lastly, rescue experiments were performed to validate the mechanism underlying the pathogenesis of PFE. Results A novel PTH1R missense mutation (c.904G > A, p.E302K) was identified in a Chinese family affected by PFE. Moreover, the E302K mutation inhibited the expression of osteogenic-specific genes and proteins in MG63 cells. Computational analysis revealed the E302K mutation decreased the binding affinity of Gαs to the PTH1R protein. Consistently, cAMP accumulation assays demonstrated that the E302K mutation impaired the intracellular PTH1-34 -induced accumulation of cAMP. Further RNA sequencing analysis and validation experiments revealed that the PI3K-AKT signaling pathway was predominantly down-regulated in response to the E302K mutation. Finally, forskolin partially restored the effects of the E302K mutation on osteogenesis. Conclusions This study indicated that the E302K mutation in PTH1R decreased the binding affinity of PTH1R protein for Gαs, down-regulated the cAMP-PI3K/AKT signaling pathway, and inhibited osteogenesis, eventually leading to PFE. This study not only expands the genotypic spectrum of PTH1R mutations but also elucidates the underlying pathogenic mechanism of PTH1R-associated PFE.
Objective:This study aimed to explore the experiences of body image changes in hematopoietic stem cell transplantation survivors in China and to depict how those changes affected their perception of self and body. Methods:A qualitative descriptive approach was applied to provide a straight and comprehensive understanding of experiences in body image changes. Twenty hematopoietic stem cell transplantation survivors who underwent transplantation at a Chinese tertiary hospital were selected through purposeful sampling. Data were collected via semi-structured interviews and analyzed using conventional content analysis. Reporting adhered to the Consolidated Criteria for Reporting Qualitative Research Checklist. Results:Three themes and 11 subthemes were identified: (1) I am an inferior person (a distinctly weird appearance, an impaired body function, and depending on external resources for survival); (2) I am a person struggling to reconcile with my changed body (struggling to conceal or disclose my changed body, negotiating the impact of my changed body on my work identity, struggling to understand and care for my changed body, and catching up in rumination over my changed body); and (3) I am a brand-new person (having escaped from the gate of hell, enhanced appearance, optimized personality, possessed sublimated emotions). Conclusions:This qualitative study offers novel insights into the experiences of body image changes in patients with hematological cancers post-hematopoietic stem cell transplantation within the Chinese context. It also presents a journey toward accepting body image changes. Further research is warranted to explore the underlying mechanisms linking body image changes to shifts in self-identity, and the process of body image acceptance.
BackgroundThe number of global hematopoietic stem cell transplantation (HSCT) survivors is increasing rapidly. Survivors encounter many challenges, but studies regarding survivorship experiences in China are scarce.ObjectivesThis study aimed to explore the survivorship experiences of Chinese patients with hematological cancers after HSCT and to describe the impact of HSCT on the survivors’ lives.MethodsDescriptive qualitative research was used. Purposive sampling was used to recruit HSCT survivors who were treated in a teaching hospital in Zhejiang Province from June 2021 to June 2022. Audio-recorded semistructured interviews were conducted, transcribed verbatim, and analyzed via conventional content analysis.ResultsFifteen HSCT survivors aged 18 to 59 years participated in this study. Four themes and 11 subthemes emerged: (1) transplant being harder than you thought (body function impaired, forced to modify diet, disturbed by survivorship uncertainty), (2) difficulty blending into circles (limited activity space, suffering from discrimination), (3) adjusting value judgment (health being a top priority, contributing to family as much as possible, feeling worthless), and (4) still being the lucky one (recovered better than others, genuine relationships acquired, self-improvement achieved).ConclusionThis study offers insight into subjective survivorship experiences of patients with hematological cancers post-HSCT within a Chinese sociocultural context and presents changed perceptions of HSCT, life alterations, adjusted value judgments, and positive self-evaluation since treatment.Implications for PracticeNurses can provide person-centered survivorship care based on the understanding of survivorship experiences of Chinese HSCT survivors. Intervention programs and informational materials should be developed to address difficulties encountered by Chinese HSCT survivors.
This study assessed the efficacy and safety between broad spectrum penicillin (P2) with or without beta-lactamase inhibitors (P2+) versus first and second generation cephalosporins (C1&C2) in the prevention of post-cesarean infections. Relevant randomized controlled trials (RCTs) were searched in English and Chinese databases: nine RCTs were involved. Six trials compared P2+ vs C1&C2, no differences were found between interventions for endometritis, wound infection, urinary tract infection, febrile morbidity and maternal rashes. Four trials compared P2 vs C1&C2, no differences were found between interventions for endometritis, febrile morbidity, wound infection and urinary tract infection. Postoperative hospitalization was longer for women in P2 than C1&C2. Based on these results, P2/P2+ and C1&C2 may have similar efficacy on postoperative infections after cesarean section, there is no data on infant outcomes. PROSPERO Registration Number: CRD42022345721.
Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.
基于血液肿瘤患者使用血管通路需求大、导管相关并发症发生率高的特点,对有关血液肿瘤患者血管通路装置的置管时机、置管部位、导管类型选择的研究文献进行综述,旨在为我国血液肿瘤患者更合理地应用血管通路装置提供参考.
Bio-ink has gradually transited from ionic-crosslinking to photocrosslinking due to photocurable bio-hydrogel having good formability and biocompatibility. It is very important to understand and quantify the crosslinking process of photocurable hydrogels, otherwise, bioprinting cannot be standardized and scalable. However, there are few studies on hydrogel formation process and its photocrosslinking behavior which cannot be accurately predicted. Herein, the photoinitiated radical polymerized bio-hydrogels are taken as an example to establish the formation theory. Three typical crosslinking reactions are first distinguished. It is further proposed that not all double-bonds consumed during crosslinking contributeequally to polymerization. Then the concept of effective double-bond conversion (EDBC) is elicited. Deriving from EDBC, several important formation indices are defined. According to theory, it is predicted that slow crosslinking can improve the crosslinking degree. Furthermore, based on the slow crosslinking effect, a new strategy of projection-based 3D printing (PBP) is proposed, which significantly improved printing quality and efficiency. Overall, this work will fill the gap in hydrogel's formation theory, making it possible to accurately quantify the formation process.
Autograft replaced by a nerve guidance conduit (NGC) is challenging in peripheral nerve injury because current NGC is still limited by precise conductivity and excellent biocompatibility in vivo, which influences the peripheral nerve repair even for a long lesion gap repair. Several particular elements have the potential function for nerve conductivity acceleration based on the traditional three factors of neural tissue engineering. The review aims to address three questions: 1) What is the superior factor for nerve conduction in the application? 2) How can a more conductive regenerative scaffold be constructed in vivo? 3) What is the next step in nerve regeneration for NGC? The bibliometrics analysis of NGC-related references is adopted to acquire that the conductive material, manufacturing technology of neural scaffold, and electrical stimulation (ES) play essential roles in the acceleration of nerve conduction. This review visually analyses the research status and summarizes the main types of conductive materials, the manufacturing technologies of neural scaffolds, and the characteristics of ES. The viewpoints and outlook of developing NGC are also discussed in this review. The proposed three elements are expected to improve the nerve conduction of NGC in vivo and even address the dilemma of long-distance peripheral nerve injury.
目的 了解经历造血干细胞移植的血液系统恶性肿瘤幸存者重返工作的体验与感受,旨在为造血干细胞移植幸存者再就业提供参考依据.方法 采用描述性质性研究方法,于 2021 年 6 月至 2022 年 4 月,基于病历记录,目的抽样曾在浙江省 1 家三级甲等医院接受造血干细胞移植后的 13 例幸存者进行半结构式访谈,通过传统内容分析法进行资料分析、归纳及提炼主题.结果 造血干细胞移植幸存者重返工作体验可归纳为 4 个主题,分别为:重返职场的时机、回归职场考虑的就业类别、再次踏入职场工作付出改变、返回职场的益处.结论 造血干细胞移植幸存者重返职场需求与体验复杂,应从多方面对幸存者重返职场体验予以关注和支持,以提高幸存者重返职场的应对能力,改善其工作体验.
Abstract Objective The purpose of this study was to investigate the effect of astilbin on pregnancy outcome in rats with recurrent spontaneous abortion (RSA). Methods A total of 40 pregnant female Sprague–Dawley rats were randomly divided into four groups: the control, model, astilbin, and prednisone groups. An RSA rat model was established by gavage with hydroxyurea and mifepristone. The number of surviving and reabsorbed embryos was counted on day 9 of gestation in each group. The rat serum was collected to detect the levels of IFN-γ, IL-2, IL-4, and IL-10 by enzyme-linked immunosorbent assay. The expressions of T-bet and GATA-3 in the decidual and placental tissues of the rats were determined by immunohistochemistry. Results The absorptivity of embryos was significantly higher in the model group than in the control group. The levels of serum IFN-γ and IL-2 were significantly lower in the astilbin group than in the model group, while the levels of serum IL-4 and IL-10 were significantly higher. Astilbin treatment significantly increased GATA-3 expression, while it significantly reduced T-bet expression and the T-bet/GATA-3 ratio. Conclusions Astilbin has a therapeutic effect on RSA in rats by regulating the balance of Th1/Th2 in maternal circulation and likely in decidual tissue.
Tissue engineering technology provides a revolutionary strategy to completely restore the structure and function of damaged tissues or organs. Digital light processing (DLP), as a kind of three-dimensional (3D) printing technology, has great advantages in printing resolution and efficiency, with low requirements for bioinks. This review introduces DLP-based printing and its development, as well as the manufacturing processes and printable materials. We also focus on tissue engineering products such as bone, tooth, cartilage, nerve, blood vessel, and so on. This review expounds on the difficulties and shortcomings of DLP printing technology in tissue engineering today. Perspectives are given on the current outlook on DLP-based 3D printing tissue engineering.
在详细检索国内外造血干细胞移植幸存者心理体验文献的基础上,从幸存者不同心理体验及相关影响因素、促进心理健康的策略两方面展开综述,基于此提出思考与启示,以期完善移植幸存者心理方面的知识,为护理人员开展移植幸存者照护提供理论依据,为后续相关科研的开展提供方向.
在详细检索国内外炎症性肠病膳食纤维文献的基础上,从炎症性肠病患者膳食纤维的摄入现状、影响因素、膳食纤维摄入量与疾病发病的关系方面展开综述,基于此提出思考与启示,以期为健康从业人员进行饮食教育提供科学的理论依据,帮助患者开展饮食实践,为炎症性肠病饮食领域医疗护理科研的开展提供方向.
目的 探究我国淋巴瘤护理研究的发展现况,揭示该领域存在的问题,以期为我国淋巴瘤护理科研的开展提供理论依据及发展方向.方法 采用文献计量法,以"淋巴瘤"和"护理"为检索词,对在中国期刊全文数据库、万方数据库和中文科技期刊全文数据库中的相关文献予以检索并分析.检索时间为各数据库建库至2019年2月.结果 共纳入淋巴瘤护理期刊文献281篇,分别发表在我国24种护理期刊上,年文献数量总体呈相对稳健上升趋势,共产生5个高频词.论文核心作者共29人,第一作者涉及全国18个省、4个直辖市和3个自治区.文献类型以经验介绍与案例报道为主,而科学研究类论文仅41篇.研究对象以成年淋巴瘤患者居多,对患儿与青少年关注不足.研究内容主要探讨治疗方案与护理经验,对患者的健康相关生活质量和心理健康状况等方面关注不够.研究机构绝大多数为医疗卫生机构,受科研资助的研究仅15篇.结论 淋巴瘤护理研究已逐渐获得我国护理同仁的关注,但研究质量有待提升,存在研究方法 单一、研究内容重复、对研究对象群体关注不足以及受科研基金资助不够等问题.为此,有必要开拓护理人员的科研思路,丰富研究方法 的学习;护理人员应根据研究问题合理运用研究方法 开展相应研究,以期加强淋巴瘤护理科研的探索及此领域高质量论文的产出,为开展优质临床护理提供理论依据,进而不断缩小国内外血液学领域护理研究的差距.