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关键词： 种植体周炎   基因多态性   遗传变异,炎症细胞因子   单核苷酸多态性   白细胞介素  

摘要： 背景:种植体周炎的发生不仅与外源性因素有关,遗传风险因素也可能会导致种植体疾病的发生,主要体现在各种细胞因子多态性引起的表达改变,因此,种植体周炎与各种相关细胞因子基因多态性的关联备受关注。目的:总结种植体周炎与多种常见相关基因多态性的相关性。方法:以“种植体周炎,种植体周围炎,种植体周围疾病,基因变异,多态性”等为中文检索词,以“peri-implantitis,genotype,SNP,Single nucleotide polymorphisms,polymorphism,variant,dental implant failures,dental implant loss”等为英文检索词,应用计算机检索中国知网、Web of Science、PubMed数据库收录的相关文献。通过阅读文题和摘要进行筛选,最终纳入65篇文献进行综述。结果与结论:白细胞介素家族(白细胞介素1、白细胞介素4、白细胞介素6、白细胞介素10、白细胞介素17)、肿瘤坏死因子α、细胞核因子κB受体活化因子/细胞核因子κB受体活化因子配体/骨保护素系统、Fcγ受体、CD14的基因多态性与种植体周炎发生的相关性尚存在争议。针对基质金属蛋白酶与种植体周炎的关系,早期研究与近年来的研究结果相反。中国人群表皮生长因子和CXC趋化因子受体2基因多态性与种植体周炎易感相关。相关性争议存在的原因主要在于样本量小、从特定地理人群收集数据的潜在局限性以及缺乏更多的具体实验证据。

关键词： 骨骼肌   骨骼肌再生   卫星细胞   细胞因子   运动   修复   炎症   综述  

摘要： 背景:卫星细胞和骨骼肌再生密切相关,当骨骼肌受到损伤或刺激时,卫星细胞能够迅速被激活并参与骨骼肌的修复过程。卫星细胞受到细胞因子的调控,而且研究表明运动能够促进卫星细胞的增殖和分化,但目前尚不清楚运动是否能够与细胞因子共同作用于卫星细胞促进骨骼肌修复。目的:综述细胞因子和运动对卫星细胞的调控作用,为肌肉疾病的治疗和康复提供新的思路和潜在的干预目标。方法:第一作者和通讯作者于2023-12-01/2024-02-01检索Web of Science、PubMed、中国知网、万方、维普等数据库,检索文献时限为各数据库建库至2024年2月。英文检索词为“skeletal muscle regeneration,satellite cells,cytokines in muscle repair,exercise,muscle stem cells,inflammation and repair”,中文检索词为“骨骼肌,卫星细胞,细胞因子,运动,肌肉再生,肌肉干细胞,炎症和修复”。最终严格按照纳入和排除标准筛选,共纳入76篇文献。结果与结论:①细胞因子在卫星细胞激活中的作用:在骨骼肌损伤后迅速激活卫星细胞,白细胞介素6促进卫星细胞增殖和迁移,从而加速肌肉的修复。肿瘤坏死因子α通过调控细胞凋亡和增殖通路,参与卫星细胞的分化和功能调节。干扰素γ则在炎症反应中发挥重要作用,调控卫星细胞参与肌肉损伤修复的免疫反应。②运动对细胞因子表达的调控作用:耐力运动和抗阻训练能够显著增加血液循环中白细胞介素6和肿瘤坏死因子α水平,进而可能促进卫星细胞的活化,参与骨骼肌再生过程。此外,运动还能增加骨骼肌分泌肌肉特异性蛋白(如肌肉生长抑制素、鸢尾素和胰岛素样生长因子1),这些因子对卫星细胞的增殖和肌肉再生具有重要调控作用。③未来研究的方向与展望:尽管已有研究揭示了多种细胞因子在卫星细胞调控中的关键作用,但相关机制仍需进一步深入探索,未来的研究可以通过整合多组学和生物信息学方法,深入解析不同细胞因子在运动促进骨骼肌损伤修复中的交互作用网络,以优化运动介入策略并提高骨骼肌再生的效率和质量。

关键词： 压应力   骨折愈合   细胞因子   骨形态发生蛋白   成纤维细胞生长因子   血小板衍生生长因子   血管内皮生长因子   白细胞介素   肿瘤坏死因子α  

摘要： 背景:骨折愈合是一个非常复杂的生理过程,受多种因素的影响。近年来运用生物力学因素在骨折愈合中展开研究是骨科领域的重点,骨折断端周围的机械应力环境对骨折愈合具有重要调控作用。其中,压应力学微环境对骨折断端细胞因子的影响机制研究是骨相关研究工作者们关注的的热点。目的:总结近年来压应力在骨折愈合中对细胞因子作用机制的研究现状和最新进展。方法:以“压应力,骨折愈合,细胞因子,骨形态发生蛋白,成纤维细胞生长因子,血小板衍生生长因子,血管内皮生长因子,白细胞介素,肿瘤坏死因子α”为中文关键词检索CNKI、万方数据库,以“Compressive stress,Fracture healing,Cytokine,Bone morphogeneticprotein,Fibroblast growth factor,Platelet-derived growth factor,Vascular endothelial growth factor,Interleukin,Tumour necrosisfactor-alpha”为英文关键词检索PubMed、Web of Science数据库,共检索到506篇文献,经筛选后对符合标准的94篇文献进行归纳分析。结果与结论:目前的研究发现,压应力在骨折愈合过程中对不同细胞因子产生不同影响,主要可通过影响细胞信号传导、基因表达调控以及细胞行为的调节等方式实现。其中,压应力可与骨形态发生蛋白、成纤维细胞生长因子、血小板衍生生长因子、血管内皮生长因子、白细胞介素、肿瘤坏死因子α等细胞因子产生作用联系,这一过程涉及到细胞的增殖分化与迁移、炎症反应应答、断端环境营养条件变化等,都是影响骨折愈合的关键因素。全文总结了细胞因子作用机制的复杂性,压应力的调控作用机制需进一步展开深入研究,并对研究中存在的问题和局限性进行思考和未来展望。

关键词： Diospyros melanoxylon   Hepatoprotective   In silico study   LC-MS   Paracetamol   Ursolic acid  

摘要： Ethnopharmacological relevance Diospyros melanoxylon , Roxb., (Ebenaceae), native to South and Southeast Asia, has been traditionally used to treat liver disorders, jaundice, tuberculosis, and chronic wounds and inflammatory conditions. Aim of the study To evaluate the hepatoprotective effect of D. melanoxylon leaf methanolic extract (MDML) in paracetamol (PCM)-induced liver toxicity in rats. Material and method Phytoconstituents in the MDML were identified via LC-MS. Molecular docking and dynamics simulations evaluated the binding stability of ursolic acid (UA) with IL-6, COX-2, and LOX. In vitro COX-2 and 5-LOX inhibition assays assessed anti-inflammatory potential. Hepatoprotective efficacy was examined in PCM-intoxicated rats treated with MDML (200, 300, 400 mg/kg). Biochemical markers, serum enzymes (ALT, AST, ALP, GGT, LDH), protein profile (TP, ALB, GLB, TB), antioxidant enzymes (SOD, CAT, GSH), oxidative stress marker (MDA), and cytokines (IL-6, IL-10, IL-1β, TNF-α) were analyzed. Histopathological examination of liver tissues further validated the findings. Result Nineteen compounds were identified by LC-MS. UA showed strong docking affinities with IL-6 (−7.0 kcal/mol), COX-2 (−8.5 kcal/mol), and LOX, with MD simulations confirming stable interactions. MDML (400 μg/mL) inhibited COX-2 and 5-LOX by 78.45 % and 85.45 %, respectively. In vivo, MDML (400 mg/kg) significantly ( p  < 0.01, p  < 0.001) reduced liver enzymes and oxidative stress markers, while improving antioxidant levels and cytokine balance. Significant reductions in TB and GLB, with corresponding increases in TP and TLB, were observed. Histology revealed dose-dependent restoration of hepatic architecture comparable to controls. Conclusion MDML shows dose-dependent hepatoprotection against PCM-induced toxicity, likely due to the presence of UA, supporting its traditional use in liver disorders.

关键词： High-altitude cerebral edema (HACE)   Hypobaric hypoxia (HH)   Musk   TNF-α/RIPK1 signaling   necroptosis  

摘要： Ethnopharmacological relevance Musk ( Moschus Moschiferus ) is regarded as a key drug for treating brain injury-related nerve damage in both traditional Chinese medicine and Tibetan medicine. According to the theory of traditional Chinese medicine, musk has the characteristics of being pungent and warm, and acts on the heart and spleen meridians, with the effects of awakening the brain and opening the orifices, as well as promoting blood circulation and removing blood stasis. This makes it an important drug for treating acute brain injuries such as closed coma and stroke with phlegm obstruction. Modern research has revealed that musk has multiple neuroprotective mechanisms and anti-inflammatory/antioxidant effects. These findings support its therapeutic potential in targeting neuronal injury pathways in the prevention and treatment of HACE, and further translational research is warranted. Aim of the study This study aimed to investigate the neuroprotective properties of musk and uncovering the mechanisms through which it may exert its beneficial effects against HACE. Materials and methods The constituents of musk were analyzed using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS)‌. Additionally, network pharmacology and proteomic profiling were applied to identify possible molecular targets and associated signaling pathways. In vivo experiments were carried out using a rat model simulating an altitude of 6000 m over a 48-h period, while in vitro investigations involved exposing cultured microglial cells to hypoxia for 6h. The effectiveness and mode of action of musk were evaluated using a range of experimental techniques, including brain water content analysis via brain water content (BWC), histopathological examination (HE), Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), transmission electron microscopy (TEM), and flow cytometry (FCM). Results The UPLC-MS analysis identified 117 active compounds within musk. The tumor necrosis

关键词： 急性淋巴细胞白血病   异基因移植   费城染色体   BCR/ABL基因   酪氨酸激酶抑制剂   微小残留病   早期干预   复发  

摘要： 背景:BCR/ABL基因是Ph染色体阳性急性淋巴细胞白血病的特异性基因,其表达水平已经成为异基因造血干细胞移植前后微小残留病监测的敏感指标。然而,移植前BCR/ABL基因表达水平是否影响移植疗效,移植后如何指导酪氨酸激酶抑制剂进行复发的早期干预尚无定论。目的:探讨Ph染色体阳性急性淋巴细胞白血病患者行亲缘间、异基因造血干细胞移植前后BCR/ABL基因表达与复发的关系。方法:选择2015年1月至2022年12月期间华北理工大学附属医院收治的24例达到血液学完全缓解后行亲缘间异基因造血干细胞移植的Ph染色体阳性急性淋巴细胞白血病患者,应用实时荧光定量聚合酶链反应动态监测治疗期间BCR/ABL基因表达水平,以此代表微小残留病。依据BCR/ABL基因表达,移植前给予酪氨酸激酶抑制剂联合化疗,选择异基因造血干细胞移植时机;移植后评估疾病状态,指导酪氨酸激酶抑制剂的应用,制定早期干预复发的方案。结果与结论:随访至2023年12月,中位随访时间为49(12-82)个月,8例血液学复发,复发的中位时间为14(8-39)个月,累积复发率为33%(8/24)。单因素分析显示,异基因造血干细胞移植后血液学复发与性别、年龄、髓外并发症、诊断至移植时间、HLA配型、急性移植物抗宿主病、慢性移植物抗宿主病无明显相关性(P>0.05);与移植前缓解疗程及微小残留病水平有明显相关性,移植前第2次血液学完全缓解、微小残留病阳性患者有更高的血液学复发率(P<0.05)。预期移植后3年累积复发率、无病生存率、总生存率分别为27%,63%,74%;5年累积复发率、无病生存率、总生存率分别为38%,57%,74%。结果表明,异基因造血干细胞移植前BCR/ABL基因阳性Ph染色体阳性急性淋巴细胞白血病患者有更高的复发率;移植后BCR/ABL基因表达可指导酪氨酸激酶抑制剂应用,做为早期干预复发的依据。

关键词： GBP1   IFN-γ   IL-2   Mycobacterium tuberculosis   Non-tuberculous mycobacteria  

摘要： Background Early differentiation between Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) is critical due to distinct treatment protocols. Traditional diagnostic methods, including acid-fast staining, bacterial culture, and nucleic acid assays, often face challenges. This study evaluated the diagnostic value of Guanylate-Binding Protein 1 (GBP1), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) in peripheral blood for distinguishing active TB, NTM infections, and cured TB. Methods We recruited patients with active TB (n = 50), NTM disease (n = 46), cured TB (n = 37), and healthy controls (HC, n = 20). GBP1 mRNA in peripheral blood mononuclear cells was quantified by qPCR. MTB-specific IFN-γ and IL-2 levels were measured by ELISA. Results The relative expression of GBP1 was significantly higher in active TB (2.764 ± 1.774) and in NTM patients (2.099 ± 0.665) compared to healthy control group (−0.001 ± 1.844; P < 0.0001 and P < 0.01, respectively). Additionally, IL-2 showed prognostic value, as levels in cured TB patients (135.7 ± 332.9) were significantly lower than in active TB patients (362.7 ± 530.7, P < 0.01). For differentiating active TB from healthy controls, the area under the receiver operating characteristic curve (AUC) for GBP1 was 0.899, outperforming IFN-γ (0.846) and IL-2 (0.786). Crucially, a combined three-marker panel demonstrated superior diagnostic performance in all comparisons, notably achieving an AUC of 0.990 for distinguishing active TB from NTM disease, significantly higher than any single marker. Conclusions GBP1 is a robust marker for identifying mycobacterial infections (both MTB and NTM). While IL-2 shows potential for monitoring treatment response, the combined detection of GBP1, IFN-γ, and IL-2 provides the highest diagnostic accuracy, effectively differentiating between NTM and MTB infections. This panel offers a promising tool for improving clinical diagnosis and patient management.

关键词： Identity leadership   Social identity   Nested organizations   Elite sports   Multigroup dynamics   Coach leadership effectiveness  

摘要： Objective This study examines how subgroups and multigroup dynamics within professional soccer clubs influence the head coach's leadership effectiveness from a social identity perspective. Design and method In this qualitative study, we conducted semi-structured interviews with 30 professional head coaches from the top four German men's leagues and the top two women's leagues. Data were analyzed using qualitative structuring content analysis and iterative abductive coding, integrating both deductive and inductive approaches, grounded in critical realism. Results The findings reveal that head coaches in professional soccer clubs operate within three key subgroups: the player group, the staff group, and the management group. Head coaches play a bridging role, unifying these subgroups as their interactions can have both positive and negative effects on their leadership effectiveness. Positive leadership experiences were characterized by functional and effective relationships ( alliances ) with at least two and often all three subgroups. In contrast, functional alliances with just one subgroup, even if it was the player group, proved insufficient and led to negative leadership experiences over time. Positive leadership experiences depended on the head coach's ability to manage the social identity dynamics within and across subgroups, as negative dynamics in any subgroup could undermine overall leadership effectiveness. These findings have been synthesized into the Multigroup Model of Identity Leadership (Multi-IL) in professional team sports. Conclusion The findings highlight the importance of considering key subgroups and their interplay for effective identity leadership. Coaches and researchers should adopt a multigroup perspective to enhance leadership effectiveness and advance leadership research.

关键词： B细胞血液恶性肿瘤   嵌合抗原受体T细胞   免疫疗法   治疗靶点   长期疗效   毒副作用   复发  

摘要： 背景:嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞疗法是治疗B细胞血液恶性肿瘤的前沿方法,其能高效且特异性地识别并杀伤肿瘤细胞,不受主要组织相容性复合体限制。目的:旨在梳理CAR-T细胞的结构、发展历程及上市产品进展,总结CAR-T细胞治疗B细胞血液恶性肿瘤的长期疗效,并探讨治疗后的毒副作用、复发性及解决策略,同时综述潜在靶点治疗B细胞血液恶性肿瘤的进展。方法:以“嵌合抗原受体T细胞,B细胞恶性肿瘤,毒副作用,免疫疗法”为中文检索词,以“CAR-T、B cell hematological malignancies,Toxic side effects,Immunotherapy”为英文检索词在中国知网、万方数据库、PubMed数据库检索CAR-T细胞相关靶点治疗B细胞恶性肿瘤的文献。结果与结论:①美国食品药品监督管理局和中国国家药品监督管理局共批准11款CAR-T细胞产品,主要针对B细胞血液恶性肿瘤的CD19和B细胞成熟抗原靶点;②长期随访数据显示,CAR-T细胞治疗为B细胞血液恶性肿瘤患者带来高缓解率和持久反应,但存在抗原丢失或下调导致的复发问题;③CAR-T细胞治疗存在高毒副作用、高复发率和耐药性等问题,限制了其广泛应用;④未来研究的方向包括开发新的靶点、联合治疗等策略,以提高CAR-T细胞的持久性和抗肿瘤活性。

关键词： Breast cancer   P18   interleukin 24   fusion protein   molecular docking   MD simulations  

摘要： Breast cancer is the second leading cause of cancer-related deaths throughout the world, and it remains one of the significant health challenges due to treatment limitations such as drug resistance and adverse side effects. Instead of developing novel treatment approaches, including radiotherapy and chemotherapy, their efficacy is trapped by non-specific toxicity and resistance. This study includes designing a novel chimeric protein combining Interleukin-24 (IL-24) and p18 peptides that are well-being to exhibit significant anticancer properties. The fusion protein, IL-24-P18, was developed to enhance specificity and minimize off-target effects in breast cancer treatment. We used silico techniques to predict this novel fusion protein construct's structural, functional and therapeutic properties. The P18 peptide was fused to the N-terminal of IL-24 using an AEAAAKEAAAKA linker. The fusion protein was found to be nontoxic, non-allergenic and non-antigenic. The fusion protein was hydrophilic with a neutral charge, exhibiting soluble expression in E. coli and stable at varying conditions. Secondary and tertiary structure predictions showed well-defined alpha-helices and a stable 3D conformation. Molecular docking and interaction analysis further confirmed strong binding affinities with a score of -847.5 Kcal/mol between IL-24-P18 and breast cancer receptor proteins, indicating the potential for selective targeting. Moreover, the MD simulation results revealed the interaction stability of the designed fusion protein and receptor. The overall results of this Insilco study showed that IL-24-P18 fusion is a prospective novel candidate against breast cancer that has the potential to inhibit breast cancer with higher accuracy and fewer side effects as compared to already available treatments. Further, in vitro and clinical studies are required to validate its clinical applicability.