巨细胞瘤,骨

摘要： 目的 探讨骨巨细胞瘤(giant cell tumor of bone,GCTB)H3.3免疫组织化学阴性病例存在的H3F3A基因突变类型.方法 收集2017年1月至2019年1月就诊于北京积水潭医院的181例GCTB,行光镜观察并结合临床影像学明确诊断.EnVision二步法免疫组织化学H3.3染色检测H3F3A G34W突变蛋白的表达,对免疫组织化学结果阴性的病例采用Sanger测序法检测H3F3A基因的突变类型.结果 免疫组织化学H3.3以细胞核阳性反应为阳性标准,181例GCTB:阳性164例,阴性17例,阳性率90.61％.对免疫组织化学结果阴性的17例采用DNA Sanger测序法检测H3F3A基因突变情况.测序结果显示8例存在突变,分别为:3例G34L(glycine 34 to leucine,3/181,1.66％),3例G34V(glycine 34 to valine,3/181,1.66％),2例 G34R(glycine 34 to arginine,2/181,1.10％),其余9例均为野生型(glycine 34,9/181,4.97％).经测序分析证实免疫组织化学H3.3阴性的病例中并无G34W突变.H3.3免疫组织化学结合测序分析,诊断GCTB总体阳性率可达95.03％.结论 H3.3免疫组织化学可检测存在H3F3A G34W突变的GCTB,对其他罕见突变类型及野生型不具诊断价值.

摘要： 目的:探讨骨巨细胞瘤(GCT)合并动脉瘤样骨囊肿(ABC)的影像学表现及鉴别特点,以提高其诊断水平.方法:回顾性分析经手术、病理证实的14例GCT合并ABC的影像学表现.所有患者均行X线检查,11例行CT检查,12例行MRI扫描,2例行全身骨显像.对其影像学表现和病理结果进行对照.结果:14例中,病灶位于股骨6例,胫骨3例,尺骨3例,腓骨1例,桡骨1例.X线及CT表现为膨胀性骨质破坏,病灶密度不均匀,皮质变薄或中断.肿瘤实质区T1WI呈等或低信号、T2WI呈以高信号为主的混杂信号,病灶内多伴囊变和液-液平面,病灶周围骨质水肿,增强扫描病灶大部分呈明显强化.全身骨现象主要表现为病变部位片状放射性核素浓聚,显影不均匀.结论:GCT合并ABC的CT、MRI表现具有一定特征,结合X线、全身骨显像检查,有助于提高该病的术前诊断准确率,为临床治疗方案的制订提供帮助.

摘要： 目的 采用有限元法分析锁定钢板复合个性化同种异体骨治疗胫骨近端骨巨细胞瘤术后骨缺损的力学参数,探讨其力学稳定性.方法 选择1例胫骨近端骨肿瘤患者,通过螺旋CT和MRI扫描获取下肢骨骼和骨肿瘤的图像数据,建立锁定钢板复合个性化同种异体骨治疗胫骨近端骨缺损的三维有限元模型,进行仿真力学分析,记录锁定钢板和个性化同种异体骨内固定物的应力分布和形变情况.结果 在模拟3倍体质量轴向载荷作用力下,锁定钢板的等效应力集中分布在与骨缺损区域相对应的钢板中段,最大应力发生在钢板近端第5枚螺钉与钉孔接触处(25.936 MPa).在轴向位移分布上,胫骨近端内侧平台、个性化同种异体骨近端在Z轴上的最大位移分别是0.293、0.272 mm;在侧方位移分布上,胫骨近端,个性化同种异体骨近端、远端在X和Y轴上的最大位移分别为0.718 mm和0.571 mm、0.668 mm和0.572 mm、0.095 mm和0.370 mm.结论 锁定钢板复合个性化同种异体骨治疗胫骨近端骨巨细胞瘤术后骨缺损,可提供有效的轴向微动和剪切力刺激,促进骨愈合,力学稳定性良好.

摘要： 目的 探讨核因子 κB受体活化因子配体(receptor activator of nuclear factor kappa-B ligand,RANKL)抑制剂denosumab治疗前后骨巨细胞瘤的临床影像学特征、组织学形态、诊断及鉴别诊断要点.方法 回顾性分析2015年3月至2017年6月11例就诊于北京积水潭医院、术前经denosumab治疗的骨巨细胞瘤病例资料,分析治疗前后影像学及组织学形态改变.结果 女性5例,男性6例,年龄20～62岁,平均年龄35岁.骶骨6例,股骨2例,桡骨、胫骨及髌骨各1例.经denosumab治疗3～6个月后,肿瘤组织学上表现为巨细胞减少甚至消失;单一性的梭形细胞增生伴不同程度的纤维化或新骨形成,骨的形态可以是幼稚的骨样基质、编织状骨及较成熟的板层骨.影像学上显示显著的骨硬化,病变周边的硬化缘形成.3例发生于骶骨的患者分别于术后5、6、11个月复发,其余术后经随访1～14个月未见复发.结论 经denosumab治疗后,骨巨细胞瘤组织形态与原病理表现截然不同,应与一些良性及恶性的骨肿瘤及肿瘤样病变相鉴别.denosumab治疗时间与形态学表现及复发情况的关系仍需进一步观察.%Objective To investigate the radiological and histopathological features of giant cell tumor of bone treated with RANKL inhibitor denosumab. Methods Eleven cases were retrieved from the surgical pathology records between March 2015 and June 2017 in Beijing Jishuitan Hospital. Formalin fixed, paraffin embedded specimens were collected and the histological features were evaluated. The imaging features including X ray, magnetic resonance imaging, and computed tomography were also reviewed. Results These 11 cases of giant cell tumor of bone were derived from five female and six male patients, with age ranged from 20 to 62 years ( mean age, 35 years). The tumors were located in the sacrum (6 cases), femur (2 cases), radius ( 1 case), tibia ( 1 case) and patella ( 1 case), respectively. Histologically, all cases showed depletion of giant cells, proliferation of mononuclear cells and different degrees of ossification 3 to 6 months after denosumab therapy. Radiography showed marked osteosclerosis and sclerotic rim formation. Three cases of the sacrum recurred after 5,6 and 11 months of surgery, and the remaining cases showed no recurrence within follow-up of 1 to 14 months.Conclusions Denosumab treated giant cell tumors morphologically differ from untreated tumors. Careful attention to a history of denosumab administration is crucial to avoid misdiagnosis and to allow proper differentiation from other tumors and tumor-like lesions.

摘要： 目的 比较不同手术方式治疗膝关节周围骨巨细胞瘤合并病理性骨折在局部复发、重建持久性及功能评价等方面的差异.方法 回顾性分析2001年1月至2014年7月在北京积水潭医院骨肿瘤科接受手术治疗的50例膝关节周围骨巨细胞瘤合并病理性骨折的患者资料.男性30例,女性20例,平均年龄为33.7岁(范围:17～71岁).骨折部位为股骨远端45例,胫骨近端5例.按照AO骨折分型,A型3例,B型36例,C型11例.Campanacci影像学分级,Ⅱ级5例,Ⅲ级45例.20例接受扩大刮除术,30例采用整块切除术.重建方式包括骨水泥填充内固定16例,单髁异体骨移植内固定5例,骨端1/2异体骨大段移植1例,人工关节置换28例.对手术情况和治疗效果进行分析,纳入性别、年龄、骨折部位、骨折分型、外科治疗方式、外科边界、重建方法、术后并发症、术后肿瘤学评价、功能评分等临床资料,用x2检验或Fisher确切概率法比较两组复发率、并发症发生率、手术方式的差异,用独立样本t检验比较组间均数差异,无复发生存分析采用Kaplan-Meier曲线,多组间均数比较采用方差分析.结果 术后平均随访时间为66.9个月(范围:24～149个月),共4例局部复发(扩大刮除组3例,整块切除组1例),扩大刮除组和整块切除组的复发率比较差异无统计学意义(P=0,289),且扩大刮除组(3/20,15.0％)与我科骨巨细胞瘤大宗无病理性骨折病例刮除复发率(10/116,8.6％)比较无差异(P=0.407).不同骨折类型复发率的差异无统计学意义(P=0.160),不同骨折类型的手术方式选择有明显差异(P=0.006).并发症情况:扩大刮除组出现并发症2例(2/20,10.0％),均为关节退变;整块切除组出现并发症15例(15/30,50.0％),其中单髁异体骨移植组异体骨吸收1例,关节置换组感染2例,无菌性松动12例(含1例合并假体周围骨折、1例合并假体断裂).两组术后并发症发生率的差异有统计学意义(P=0.005).扩大刮除组和整块切除组术后MSTS功能评分分别为(93.5±6.5)％和(82.6±12.9)％,差异有统计学意义(F=4.838,P=0.033).结论 扩大刮除术不增加膝关节周围骨巨细胞瘤合并病理性骨折的复发风险.不同骨折类型对复发率无影响,但骨折类型影响手术方式的选择.整块切除术后并发症发生率高于扩大刮除组,扩大刮除组术后功能优于整块切除组.%Objective To compare the local recurrent rate,the persistence of reconstruction and functional recovery of Giant Cell Tumor (GCT) after the treatments of extensive curettage or resection.Methods A retrospective review was conducted on the clinical data of 50 patients who had giant cell tumor with pathological tracture around the knee treated in our hospital from January 2001 to July 2014.There were 30 males and 20 females.The average age was 33.7 years respectively (range,17 to 71 years).The fracture localizations of 45 cases were distal femur and of 5 cases were proximal tibia.According to AO fracture classification,3 cases were in type A,36 cases in type B and 11 cases in type C.In Campanicci system for image grading study,5 cases were in grade Ⅱ and 45 cases in grade Ⅲ.Surgical treatment included 20 cases of extensive curettage and 30 cases of resection.The surgical reconstructive methods included 16 cases of cement reconstruction with internal fixation,5 cases of unicompartmental arthroplasty with allograft,1 case of segment osteoarticular allograft transplantation and 28 cases of prosthesis replacement.Final statistical analysis of surgery and therapeutic effect were carried out by SPSS,version 16.0 for Windows.Enrolling parameters collected gender,age,location,fracture type,surgical treatment,surgical margin,reconstruction,complications,local recurrence (LR) and functional evaluation.Categorical data were described by result frequencies.The comparison of the rate was performed by chi-square or Fisher's exact test.Between the two groups compared using independent t-test.The recurrence-free survival was estimated by the method of Kaplan-Meier.Results The mean postoperative follow-up time was 66.9 months (range,24-149 months).Four patients developed local recurrence (4/50,8.0％) including 3 cases of curettage group (3/20,15.0％)and 1 case of resection group (1/30,3.3％),there was no significant difference between curettage and resection group (P =0.289).The comparison of local recurrence between this curettage group (3/20,15.0％) and the GCT group without fracture published before (10/116,8.6％) in our institution also had no significant difference (P =0.407).There was no significant difference among the three types of fracture regarding the rate of local recurrence (P=0.160),but there was significant difference in the choice of surgical procedures for different fracture types (P =0.006).The complications:2 patients (2/20,10.0％)had joint degeneration in curettage group.15 cases (15/30,50.0％) had complications in resection group,1 case of unicompartmental arthroplasty allograft absorption,2 cases of infection and 12 cases of aseptic loosening after prosthesis replacement (including 1 case with periprosthetic fracture and 1 case with prosthesis fracture).The postoperative complications in curettage group had a significant reduction (P =0.005) when compared with the resection group.The mean score of functional evaluation with Musculoskeletal Tumor Society (MSTS) for curettage and resection group were (93.5±6.5)％ and (82.6± 12.9)％ (F=4.838,P=0.033).Conclusions (1) Extensive curettage did not increase the risk of local recurrence of giant cell tumor with pathological fracture around the knee.(2)The different fracture type had no effect on the local recurrence rate,but affect the decision of surgical procedures options.(3)The reconstructive complications in resection group was significant higher than curettage group,and the postoperative function of curettage group was better than resection group.

摘要： 目的 探讨核心结合因子(RunX2)表达与骨巨细胞瘤(GCT)临床病理特征之间的关系.方法 选择GCT标本58例,分别按照肿瘤恶性程度、肿瘤病理分级、是否侵犯软组织及是否伴发病理性骨折分组,应用免疫组织化学染色技术分析并比较RunX2在不同组表达水平的差异.结果 RunX2在恶性GCT组织内的表达水平显著高于良性GCT组织(P＜0.05);RunX2的表达随着GCT组织分级的升高而升高(P＜0.05);有软组织侵犯状况的GCT组织内的表达RunX2水平高于无软组织侵犯GCT组织(P＜0.05);而伴发病理性骨折的GCT组RunX2表达量高于无伴发病理性骨折组(P＜0.05).结论 RunX2的表达量与GCT严重程度有关.%Objective To explore the relationship between the RunX2 expression and the clinicopathological features in bone giant cell tumor(GCT).Methods Fifty-eight specimens of GCT were selected and grouped according to the malignant degree,tumor pathological grade,whether having soft tissue invasion and complicating pathological fracture.Then the immunohistochemical staining technique was used to analyze and compare the difference of RunX2 expression levels among different groups.Results The RunX2 expression level in malignant GCT tissues was significantly higher than that in benign GCT tissue(P＜0.05).RunX2 expression level was increased with the GCT tissue histological grade increase(P＜0.05).The expression level RunX2 in GCT tissue with soft tissue invasion was significantly higher than that in the GCT tissue without invasion(P＜0.05);the RunX2 expression level in GCT tissue with complicating pathologic fractures was significantly higher than that in the GCT tissue without complicating pathologic fractures(P＜0.05).Conclusion The RunX2 expression level is related to the severity of GCT.

摘要： Objective To evaluate the safety and efficacy of denosumab in treatment of patients with pelvic giant cell tumor of bone (GCTB) during perioperative period. Methods This is a retrospective observational study. Twenty-three patients diagnosed with pelvic GCTB undergoing perioperative denosumab treatment in Musculoskeletal Tumor Center of Peking University People's Hospital from January 2014 to December 2016 were reviewed. The subjective adverse reactions and mandibular X-ray films were used to assess the drug safety. As for efficacy, imaging findings (including X-ray, CT, magnetic resonance imaging) were reviewed. MSTS-93 scoring system was applied in the postoperative functional assessment. Histological response rate, objective response rate, clinical benefit rate and event-free survival rate were all used to deficit the efficacy of denosumab in the treatment of pelvic GCTB combined with surgery. All the results of postoperative were compared statistically with pelvic GCTB patients who underwent surgery in the same hospital from 1999 to 2009. Results All the patients were firstly diagnosed as classic GCTB except for one case which was malignant pelvic GCTB. All patients received denosumab preoperatively and/or postoperatively, and the average number of medications was 8.43. According to the surgical patterns, patients were divided into intralesional surgery group (13 cases) and wide resection group (10 cases). The follow-up was 5-47 months(mean:27.30 months),recurrence was observed in 2 cases in the intralesional surgery group, none in the wide resection group. After drug administration, 13 cases were partial response, 7 cases were stable disease, the objective response rate was 65.0 % (13/20), and the histologically clearance rate of giant cells was 85.0 % (17/20). No case of osteonecrosis of the jaw was observed in this study, and all laboratory indicators were normal. The average postoperative MSTS-93 score was 26.87. Compared with pelvic GCTB patients who underwent surgical treatment from 1999 to 2009, in the intralesional surgery group, there was no significant difference in the recurrence rate [15.4 % (2/13) vs. 30.8 % (4/13), P = 0.514], but the limb function was significantly increased (P= 0.002). Conclusions Denosumab combined with surgery plays an important role in the multidisciplinary treatment of pelvic GCTB. The neoadjuvant strategy can reduce patient's intraoperative blood loss by shrinking the tumor size which makes the intralesional curettage surgery possible, and also diminishing the recurrence rate. But more attention should be paid to secondary malignant GCTB during the use of denousmab.%目的 探讨围术期应用地诺单抗治疗骨盆骨巨细胞瘤(GCTB)的有效性和安全性.方法 回顾性分析2014年1月至2016年12月北京大学人民医院骨与软组织肿瘤治疗中心23例在围术期接受地诺单抗治疗的骨盆GCTB患者临床资料.采用主观不良反应、下颌骨X线片等指标评估安全性,采用X线、CT和磁共振成像(MRI)等常规影像学指标评估有效性.基于美国骨肿瘤学会(MSTS)-93评分评估术后功能.肿瘤学评估指标包括组织学反应率、客观反应率、临床受益率、无事件生存率等.术后功能与1999年至2009年在该中心接受外科治疗的骨盆GCTB患者进行统计学比较.结果23例患者初诊活组织检查均证实为GCTB,其中1例提示为恶性GCTB,同时伴有肺转移.全部患者均接受外科治疗,达到广泛外科边界10例,囊内或边缘切除13例.所有患者均按计划用药,平均用药8.43次.随访5~47个月,平均27.3个月,2例患者死于肿瘤进展.广泛切除组中无局部复发,囊内刮除组2例术后复发.术前用药后疗效评估显示部分缓解13例,疾病稳定7例,客观反应率65.0 %(13/20),组织学巨细胞清除率85.0 %(17/20).用药期间未出现下颌骨坏死病例,实验室安全性指标均未见异常.患者术后MSTS-93功能评分平均为26.87分.与1999年至2009年在该中心接受外科治疗的骨盆GCTB患者比较,囊内刮除组术后复发率差异无统计学意义[15.4 %(2/13)比30.8 %(4/13),P=0.514];累计髋臼病例术后功能较1999年至2009年组提高(P=0.002).结论 地诺单抗是治疗骨盆GCTB的有效手段,术前用药在缓解症状的同时,可使肿瘤血供减少、体积缩小,降低手术难度.术后用药可能会降低囊内刮除手术的复发风险,继发恶性变是值得关注的问题.

摘要： 目的 观察可动脊柱浆细胞瘤与骨巨细胞瘤的影像学表现,剖析鉴别诊断要点.方法 回顾性分析经病理证实的39例浆细胞瘤(浆细胞瘤组)和34例骨巨细胞瘤(骨巨细胞瘤组)患者的临床及影像学资料.结果 2组患者年龄差异有统计学意义(t=11.63,P＜0.001),性别差异无统计学意义(x2=0.013,P=0.91).34例浆细胞瘤和26例骨巨细胞瘤的骨质破坏主体位于椎体;1 3例浆细胞瘤和20例骨巨细胞瘤表现为膨胀性骨质破坏;5例浆细胞瘤和12例骨巨细胞瘤可见硬化边;2例浆细胞瘤和10例骨巨细胞瘤合并骨质硬化;12例浆细胞瘤和15例骨巨细胞瘤内可见残存骨棘;24例浆细胞瘤和19例骨巨细胞瘤合并压缩骨折;15例浆细胞瘤和21例骨巨细胞瘤突破骨皮质在硬膜外形成软组织肿块,其中13例浆细胞瘤和2例骨巨细胞瘤软组织肿块包绕脊髓生长.2组肿瘤骨质破坏形式、是否有硬化边、合并骨质硬化、是否形成硬膜外软组织肿块及软组织肿块是否包绕脊髓生长的差异均有统计学意义(P均＜0.05),而肿瘤骨质破坏主体部位、合并残存骨棘及压缩骨折发生率差异均无统计学意义(P均＞0.05).结论 可动脊柱浆细胞瘤与骨巨细胞瘤的影像学表现具有相似性,需结合肿瘤骨质破坏形式、骨质破坏周围硬化边、合并骨质硬化及硬膜外软组织肿块及其包绕脊髓生长情况进行鉴别诊断.

摘要： 本发明公开了一种与巨细胞病毒具有特异性的巨细胞抗体适配子，同时利用该巨细胞抗体适配子构成的生物芯片。本发明与传统检测技术中的抗体相比，寡核苷酸适配子还具与靶分子结合力更强、稳定性好、精确性高、重复性好、可反复使用、可长期保存、可进行精确的位点修饰、筛选期更短等优势；所得到的生物芯片放入SPR生物传感器检测，能实现(1)实时检测、(2)无需标记样品、(3)样品需要量极少、(4)检测过程方便快捷，灵敏度高、(5)应用范围非常广泛、(6)高通量、(7)大多数情况下、(8)能检测混浊的甚至不透明的样品。

摘要： 本发明公开了一种骨巨细胞瘤挖除术后骨缺损部位填充物，其包括镁合金基体以及设于所述镁合金基体表面的钙磷涂层，所述钙磷涂层上负载有双磷酸盐。本发明还公开了一种骨巨细胞瘤挖除术后骨缺损部位填充物的制备方法。本发明的骨巨细胞瘤挖除术后骨缺损部位填充物以镁合金材料为基体，其上设置钙磷涂层和双磷酸盐双膜层，将其作为骨巨细胞瘤挖除术后瘤腔填充物，可达到病灶处药物释放的目的，实现双磷酸盐类药物抑制肿瘤缺损处骨破坏，防止骨吸收的效果，同时达到可降解镁合金修复骨缺损的效果，可以治疗骨巨细胞瘤术后骨缺损的重建，降低肿瘤复发率。

摘要： 本发明公开了一种与弓形虫病毒具有特异性的弓形虫抗体适配子，同时利用该弓形虫抗体适配子构成的的生物芯片。本发明与传统检测技术中的抗体相比，寡核苷酸适配子还具与靶分子结合力更强、稳定性好、精确性高、重复性好、可反复使用、可长期保存、可进行精确的位点修饰、筛选期更短等优势；所得到的生物芯片放入SPR生物传感器检测，能实现(1)实时检测、(2)无需标记样品、(3)样品需要量极少、(4)检测过程方便快捷,灵敏度高、(5)应用范围非常广泛、(6)高通量、(7)大多数情况下、(8)能检测混浊的甚至不透明的样品。

摘要： 本发明属于医疗工程技术领域，提供了一种用于治疗骨巨细胞瘤的瘤腔填充物及其制备方法，该混合物将二磷酸盐类药物和骨水泥按照比例混合，将骨水泥作为二磷酸盐类药物的缓释载体，形成一种局部给药系统，其原理是通过骨水泥作为药物释放载体，将二磷酸盐类药物释放于病灶处，以达到病灶处于一个长时间、高浓度的药物环境的目的，从而提高二磷酸盐类药物抑制骨破坏，防止骨吸收的效果，同时不影响骨水泥修复骨缺损的作用。

摘要： 一种人原代骨巨细胞瘤细胞株GCTB28‑luc及其构建方法和应用，所述人原代骨巨细胞瘤细胞株GCTB28保藏于中国典型培养物保藏中心，地址：中国武汉市武汉大学，保藏号为CCTCC NO：C2018178。本发明构建的细胞株GCTB28‑luc具有人原代骨巨细胞瘤肿瘤细胞的特性，符合建系标准，可在培养基中进行体外培养，且体外培养生长稳定、能连续传代，进而方便可用于建立骨巨细胞瘤发生机理模型，可作为骨巨细胞瘤发病机制及个体化治疗体外研究的细胞材料，可应用于制备、筛选、评价抗骨巨细胞瘤药物。

摘要： 本发明公开一种人骨巨细胞瘤细胞株及其应用，该人骨巨细胞瘤细胞株为人骨巨细胞瘤细胞株GCT-WFCCTCCNO.C2012101，可以用于在细胞水平上研究骨巨细胞瘤的发生、发展和转移的机理，建立骨巨细胞瘤动物模型，并将其作为靶标筛选抗癌药物。

摘要： 本发明提供含有非甾体抗炎剂或噻唑烷衍生物作为有效成分的骨·软组织中产生的巨细胞性肿瘤或软骨肉瘤的预防或治疗剂等。

摘要： 本发明提供含有非甾体抗炎剂或噻唑烷衍生物作为有效成分的骨·软组织中产生的巨细胞性肿瘤或软骨肉瘤的预防或治疗剂等。

摘要： 本发明提供一种miRNA‑217促进剂在制备抗癌药物中的应用，所述miRNA‑217促制剂能够促进癌细胞中miRNA‑217的表达；所述miRNA‑217促进剂能够促进癌细胞中抑癌因子E‑cadherin的表达，同时抑制癌细胞中N‑cadherin和Vimentin的表达；所述miRNA‑217促进剂还包括OPG/RANK/RANKL信号通路抑制剂，所述OPG/RANK/RANKL信号通路抑制剂能够促进癌细胞中OPG的表达，同时还能够抑制癌细胞中RANK和RANKL的表达；所述癌细胞包括但不限于骨巨细胞瘤细胞、胃癌细胞、前列腺癌细胞和骨肉瘤细胞。本发明通过实验验证了miRNA‑217促进剂在制备抗癌药物，尤其是制备抗骨巨细胞瘤药物方面具有非常好的应用前景。

摘要： 本发明提供一种miRNA‑217抑制剂作为抗骨巨细胞瘤药物的应用，所述miRNA‑217抑制剂通过下调miRNA‑217的表达，促进骨巨细胞瘤中GCT0404细胞自噬，从而抑制骨巨细胞瘤的增殖实现其抗骨巨细胞瘤的作用。