睾丸生殖细胞瘤基因组学研究进展

睾丸生殖细胞瘤(TGCT)是最常见的睾丸恶性肿瘤,发病率逐年升高。然而,睾丸肿瘤的发病原因及机制尚未明确,新兴的第2代测序技术(NGS)已成为TGCT发病机制研究的主流手段。本文将对多年来TGCT基因组学研究进行总结,以便从基因层面上揭示该肿瘤的发病机制。总结发现基因表达差异、基因突变、易感基因主导的信号通路及性染色体上相关基因的改变在TGCT发生、发展过程中起到重要作用。睾丸肿瘤的基因组学研究意义重大,找出关键致病基因,为从基因水平上早期诊断筛查及后续的靶向治疗提供理论基础。     

重视精准智慧医疗研究, 积极应对骨肿瘤诊治发展趋势

自实施以手术为主的综合疗法以来, 骨肿瘤的诊断方法和治疗水平有了很大的进步和突破。原发性恶性骨肿瘤的生存率明显提高, 如骨肉瘤五年生存率从原来的5%～20%提高至60%～70%。骨肿瘤的特点是:(1)发病部位广;(2)肿瘤类型多;(3)肿瘤异质性高;(4)结构和功能重建并重;(5)转移性肿瘤多于原发性肿瘤。基于上述特点, 骨肿瘤的诊断须遵循临床、影像、病理三结合的基本原则;在遵循肿瘤切除原则达到局部控制的基础上, 还要进行有效的骨与软组织结构性缺损重建和获得尽量完美的运动功能。由于基因研究、生物信息技术、数字医学及计算机技术的发展, 骨肿瘤的诊疗已经进入具有精确、准时、共享和个体化四大特征的精准医学阶段。利用基因组学、转录组学、蛋白组学和代谢组学等技术探索骨肿瘤发生、发展机制, 寻找新靶向基因, 为未来精准医疗在骨肿瘤中的应用提供了方向。应用基于人工智能的智慧医疗对骨肿瘤的辅助诊断和精准治疗具有重要意义。     

骨巨细胞瘤及其辅助治疗研究现状

骨巨细胞瘤(GCTB)是一种常见的局部侵袭性原发性骨肿瘤,好发于20~40岁人群的长骨骨端,生物学行为存在不确定性,局部复发率较高。临床上主要采取囊内刮除和节段切除手术治疗,其中囊内刮除结合各种物理和化学辅助疗法可提高肿瘤局部控制效果,降低肿瘤复发率。该文在复习GCTB流行病学特点、分级与诊断、手术治疗等的基础上重点综述高速磨钻技术、温度消融技术(氩气刀、微波、液氮、氩氦刀)、骨水泥填充以及化学辅助剂(如苯酚、高浓度酒精)辅助治疗的应用现状,以期对GCTB辅助治疗的选择提供参考。     

IgA肾病发病机制的研究进展

IgA肾病(IgA nephropathy, IgAN)是目前全球范围内最常见的原发性肾小球肾炎, 20%～40%的患者在诊断后20年内进展为终末期肾病。IgAN的发病机制尚不明确, 临床治疗主要以控制病情进展为主, 缺乏特异性治疗方案。围绕半乳糖缺乏的IgA1(galactose-deficient IgA1, Gd-IgA1)开展的一系列研究提示IgAN发病涉及多个环节。该文从IgA1的结构特征、IgAN患者体内Gd-IgA1抗体及含Gd-IgA1免疫复合物、Gd-IgA1免疫复合物在肾脏中的沉积、Gd-IgA1免疫复合物沉积对肾脏的损伤、补体在IgAN中的作用、IgA肾病的基因组学及黏膜免疫与IgAN等方面, 综述了IgAN发病机制的研究进展, 为进一步的研究和临床治疗提供线索和思路。     

<中国矫形外科杂志>1999年主要刊文综述

《中国矫形外科杂志》(以下简称本刊)1999年共发表论文662篇,重点刊出了脊柱四肢骨疾病、骨创伤、骨肿瘤、先后天性肢体畸形矫治及骨科领域基础研究等方面的论文,基本反映了我国矫形外科诊治和基础研究的现状与水平。1　骨肿瘤本刊1999年第1、8期重点报道了骨肿瘤诊断、治疗、基础研究及治疗进展。1.1　骨肿瘤诊断方面医学影像检查方法的选择及其结果的评价对早期诊断椎管内肿瘤十分重要,叶根茂等(8:568)将73例经手术治疗、病理证实的原发性椎管内肿瘤的资料进行分析,发现椎管造影、ＣＴＭ、ＭＲＩ确诊率高,Ｘ线平片和ＣＴ则较低,认为在神经…     

胫骨远端骨巨细胞瘤临床特点和外科治疗的研究进展

<正>骨巨细胞瘤(giant cell tumor of bone, GCTB)是好发于青壮年患者的原发良性骨肿瘤,虽然病理学表现为良性,但临床和影像学均有明显的侵袭性表现^[1]。GCTB的最常见发病部位是股骨远端和胫骨近端,其他好发部位包括股骨近端、桡骨远端和肱骨近端,也可发生于脊柱、骶骨和骨盆等中轴骨部位^[2]     

CD34、MMP-9、VEGF、PCNA在骨巨细胞瘤中的表达及临床意义

目的探讨CD34、基质金属蛋白酶(MMP-9)、血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA)在骨巨细胞瘤(GCTB)组织中的表达及其临床意义,为GCTB的诊断与治疗提供临床依据。方法将2010年1月至2017年1月收治的80例GCTB手术患者纳入研究,采用免疫组化染色法检测GCTB组织中CD34、MMP-9、VEGF、PCNA的表达水平,分析其与GCTB患者年龄、性别、肿瘤大小、Jaffe分级以及预后之间的相关性。结果CD34、MMP-9、VEGF、PCNA的阳性表达与GCTB患者年龄、性别无明显相关性(P0.05),与肿瘤大小、Jaffe分级、预后有显著相关性(P0.05)。CD34与MMP-9、VEGF、PCNA的表达呈正相关(r=0.311,0.424,0.401;P=0.015,0.025,0.025)。结论 CD34、MMP-9、VEGF、PCNA在GCTB的发生发展中有重要作用,检测其表达水平对GCTB的诊断和预后具有一定的临床意义。     

ARDS发病机制和治疗研究新进展

在未来急性呼吸窘迫综合征(ARDS)发病机制及治疗研究中,遗传学与分子生物学领域的研究将起到重要作用,集中在基因组学、微排序技术及基因突变等方面,这对理解ARDS病人的个体生物特性及向其提供个性化治疗具有重要意义     

ARDS发病机制和治疗研究新进展

在未来急性呼吸窘迫综合征(ARDS)发病机制及治疗研究中，遗传学与分子生物学领域的研究将起到重要作用，集中在基因组学、微排序技术及基因突变等方面，这对理解ARDS病人的个体生物特性及向其提供个性化治疗具有重要意义。     

Peyronie病的研究进展

在近 30年里 ,派罗尼病 (Peyronie’sdisease)的发病率有上升趋势。由于对疾病基础知识的研究 ,以及早期诊断、药物治疗和外科技术的改进 ,目前 ,本病的治疗方法众多 ,预后也明显改观 ,仅有少数患者将阴茎假体手术作为唯一的治疗选择。本文就关于派罗尼病的发病机制、病理、诊断和治疗等作一综述。     

Reconstruction with β-tricalcium phosphate for giant cell tumor of the talus

Giant cell tumor of bone (GCTB) is a locally aggressive tumor, commonly occurs in the long bones, and is rare in the talus and the foot. The talus is a weight-bearing bone and strut reconstruction is preferred. Reconstruction with low porosity β-tricalcium phosphate (β-TCP) blocks is reported for GCTB in the knee. In the current report, a 25-year-old female suffered from GCTB in the talus extending to the subchondral bone. The tumor was treated by curettage and the bone was reconstructed with low porosity β-TCP blocks, which have strong compressive strength. The implanted β-TCP blocks were incorporated successfully. The current reconstruction method can be applied for GCTB in the talus.     

Unusual presentation in Haiti of a recurrent giant cell tumor of bone affecting the distal radius: A case report

IntroductionGiant cell tumor of bone (GCTB) is a benign-aggressive tumor that has a high-rate of recurrence with curettage resection alone. Patients with GCTB in underserved regions of the world can have progression of the tumor with significant disability due to a lack of specialty care. We present a case of an en bloc resection of an aggressive, recurrent GCTB of the radius with excellent function and no evidence of tumor recurrence two years after surgery.Presentation of caseA 22-year-old right-hand dominant female in Haiti developed an aggressive recurrence of a giant cell tumor of bone (GCTB) of the distal radius. Treatment consisted of en bloc resection of the distal radius with the proximal row of the carpus and centralization of the ulna. At two-year follow-up, the patient maintained good functional capacity with no clinical or radiological evidence of recurrence.DiscussionGCTB can cause significant destruction of the bone and articular surface if not treated adequately. Treatment options should be considered carefully in underserved regions of the world based on the resources available. This case exemplifies that complex limb-salvage surgery is possible when coordination of care between international and local surgeons is provided with an emphasis on continuity of care post-operatively.ConclusionEn bloc resection with centralization of the ulna remains a viable technique to address aggressive GCTB of the distal radius and can be appropriate in resource-limited settings.     

骨巨细胞瘤治疗新突破——狄诺塞麦

骨巨细胞瘤（GCTB）是一种富含巨细胞的侵袭性、溶骨性病变,特征为大量多核破骨细胞样巨细胞聚集、表达细胞核因子JCB受体活化因子配体（RANKL）,目前还没有一种方法可彻底有效治愈,尤其是对无法手术的GCTB。近年文献报道在进行性或无法手术的GCTB患者中使用狄诺塞麦（denosumab）,可观察到肿瘤成分明显改变、骨破坏减少及临床有效性。狄诺塞麦是一种人RANKL单克隆抗体,与核因子wB受体活化因子（RANK）结合具有很高的亲和性和特异性。以往很多大规模Ⅲ期试验研究已表明,狄诺塞麦在降低各种肿瘤引起的骨破坏方面明显优于二磷酸盐,还可延缓骨转移出现。该文对相关文献进行回顾,并就狄诺塞麦在GCTB治疗中存在的问题进行探讨。     

Cytokines Expressed in Multinucleated Cells: Paget's Disease and Giant Cell Tumors versus Normal Bone

Human osteoclasts are well characterized multinucleated cells whose function is the directed resorption of normal bone (NB). Osteoclastic bone destruction accompanies lytic solid tumors and myeloma as well as Paget's disease (PD) of bone and giant cell tumors of bone (GCTB). The mechanism of this stimulation of osteoclastic bone resorption is unknown. This study was designed to detect cytokines present in the multinucleated cells of PD and GCTB in order to determine whether cytokine abnormalities exist to account for bone lysis. Nine cytokines, representing the functions of bone resorption, angiogenesis, tumor necrosis, bone cell proliferation, and osteoblast–osteoclast coupling, were examined by immunohistochemistry using tissue samples from 15 NB, 17 PD, and 19 GCTB patients. Standard nonparametric statistical analysis showed a significant increase (P < 0.01 to 0.05) in immunostaining between osteoclasts of PD and NB for interleukin-6 (Il-6), tumor necrosis factor beta (TNFβ), epidermal growth factor (EGF), platelet derived growth factor (PDGF), and basic fibroblast growth factor (bFGF). There was a statistically significant decrease in immunostaining of giant cells of GCTB as compared with NB for transforming growth factor beta (TGFβ), but no other differences from normal osteoclasts. The increase in staining of PD osteoclasts over the giant cells of GCTB was significant (P < 0.01) for Il-6, TNFβ, PDGF, bFGF and insulin growth factor-1 (IGF-1), and (P < 0.05) for Il-1 and EGF. It was concluded that marked cytokine differences exist in vivo between osteoclasts of NB and PD lesions consistent with stimulated resorption. Alternatively, ``osteoclastoma' cells in the center of the tumor did not overexpress the cytokines associated with bone lysis, suggesting some other mechanism for stimulated resorption. Received: 12 February 1996 / Accepted 31 December 1996     

Multicentric giant cell tumor of the fourth and fifth metacarpals with lung metastases

Giant cell tumors of bone (GCTB) are generally benign neoplasms, but recently, some authors consider them to be low-grade malignant neoplasms because they have a relatively high rate of recurrence and at least some potential for metastases. The majority of GCTB are unifocal, and less than 1 % are multicentric. We report a rare case of a multicentric GCTB arising simultaneously in the non-dominant fourth and fifth metacarpals of a 25-year-old female. The patient underwent ray amputation of the two involved digits, and the surgical margins were histologically negative for tumor. The tumor had the classic histologic appearance of a benign GCTB. A year after the amputation, the patient developed pulmonary metastasis which was treated with pulmonary lobe resection. She is currently over 2.5 years postsurgical treatment of the primary lesion with no evidence of local recurrence or distant metastasis.     

CD33+ CD14− Phenotype Is Characteristic of Multinuclear Osteoclast‐Like Cells in Giant Cell Tumor of Bone

Giant cell tumor of bone (GCTB) is a benign bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. GCTB is composed of uniformly distributed osteoclastic giant cells, thought to originate from the fusion of monocyte–macrophage lineage cells, in a background consisting of mononuclear rounded cells and spindle‐shaped cells. Several reports showed the specific expression of markers, such as CD14 on the mononuclear rounded cell population, however, lacking osteoclastic giant cells. Blood monocytes that were CD14+, CD33+, or CD14+/CD33+ have also been shown to be programmed as pre‐osteoclasts. The macrophage marker CD33 is expressed earlier than CD14 in macrophage maturation, whereas CD14 is expressed longer than CD33. The aim of this study was to investigate CD14/CD33 expression profiles in GCTB. Nineteen GCTB tumor samples of 19 patients were studied. Immunofluorescent analyses were performed with monoclonal antibodies against CD14, CD33, RANK, and CD51. To unambiguously further prove the expression of these molecules, quantitative RT‐PCR was used with subsequent sequencing of its products. All samples showed similar immunoreactivity profiles. The mononuclear rounded cell population was positive for RANK, CD51, CD14, and CD33. The osteoclastic giant cell population expressed RANK and CD51, as well as CD33, but was consistently negative for CD14 expression. The CD14 and CD33 profiles were confirmed by quantitative RT‐PCR. These RT‐PCR products were sequence verified. Osteoclasts in GCTB are the result of fusion of CD33‐expressing pre‐osteoclasts that further fuse with CD14+ mononuclear cells. Although these results reflect a static rather than a dynamic spectrum, we strongly believe that osteoclastogenesis seems not to be the exclusive result of fusion of intratumoral CD14+ mononuclear cells. Moreover, CD33‐modulated osteoclastogenesis opens up the possibility for novel therapeutic directions.     

Present day controversies and consensus in curettage for giant cell tumor of bone

BackgroundThe ideal treatment for giant cell tumor of bone (GCTB) is still controversial. The purpose of this study was to evaluate whether curettage was successful in the treatment of GCTB. Intralesional curettage with adjuvant therapies, such as high-speed burring, polymethylmethacrylate, phenol, ethanol, and liquid nitrogen, may be used to reduce the local recurrence rate. However, there is no consensus on the optimal use of curettage, along with fillers and adjuvants, to limit the recurrence rate.MethodsWe performed a systematic review of articles using the terms long bones, GCTB, and treatment. Case reports, reviews, opinion articles, or technique notes were excluded based on the abstract. Twenty-six articles included in this review were then studied to establish the index in suggesting the surgical treatment of GCTB.ResultsThe patient’s gender, their age, the Campanacci grade of their tumor, and the type of surgery they had were not significantly associated with the local recurrence rate. Local recurrences seemed to be associated with the site of the tumor, occurring more frequently in the proximal femur or distal radius. A pathological fracture was not a contraindication for intralesional curettage. Treatment with denosumab did not decrease the local recurrence rate in patients who had been treated with curettage.ConclusionThe current literature seems to suggest that the ideal treatment for GCTB is to remove the tumor while preserving as much of the joint as possible. Local recurrent tumors can be treated with curettage to keep the re-recurrence rate within an acceptable limit. The choice for how to treat GCTB in the proximal femur or distal radius requires special attention.     

骨质疏松受体基因研究方向

骨质疏松症(osteoporosis)是一种以骨量低下、骨组织微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病。骨质疏松是多因素、多基因疾病,是遗传和环境因素交互作用的结果。笔者论述了降钙素受体基因、甲状旁腺素受体基因、雌激素受体基因、肿瘤坏死因子基因、胰岛素样生长因子1受体基因、骨保护素基因、转化生长因子基因、维生素D受体基因、Ⅰ型胶原蛋白基因的生物学特征及其与骨密度、骨质疏松、骨质疏松性骨折的关联,为骨质疏松的发病机制、预防治疗、新药开发研究提供分子生物学依据。     

骨巨细胞瘤干细胞的分离鉴定

目的 探索从骨巨细胞瘤（giant cell tumor of bone,GCTB）中分离肿瘤干细胞的方法.方法 对临床GCTB患者的手术标本进行原代培养,并对获得的细胞株进行特定条件下的培养获得球体细胞,在此基础上对球体细胞进行自我更新能力和干细胞相关基因检测,并通过免疫缺陷小鼠对该亚群致瘤能力进行评价.结果 从GCTB中分离出表达干细胞相关基因的球体细胞群,该球体细胞群高表达干性基因OCT4、NANOG、SOX2,具备更强的侵袭性,动物实验表明球体细胞致瘤能力比原代细胞更强.结论 GCTB中存在肿瘤干细胞,可成功进行分离鉴定,在此基础上对该亚群的生物学特性进行的初步探索,为将来进一步的研究和寻找临床治疗方法提供了理论基础.