OBJECTIVE:Versican (VCAN), a member of the multifunctional glycoprotein family, is involved in various aspects of cancer progression. However, the role of VCAN in diverse cancers remains poorly defined. This research aimed to investigate the correlation between VCAN expression and the oncogenic role, as well as visualize its prognostic landscape in pan-cancer.METHODS:Raw data in regard to VCAN expression in cancer patients were acquired from GEO GeneChip public database in NCBI. Besides, we selected microarray data GSE16088 for analysis. We retrieved the genes associated with osteosarcoma (OS) from the OMIM database and identified their intersection with the core module. VCAN was suggested to be a potential marker gene for OS. Subsequently, we conducted Gene Set Enrichment Analysis (GSEA) to explore gene functional enrichment. Moreover, we performed pan-cancer analysis on VCAN to gain a comprehensive understanding of its implications across various cancer types.RESULTS:The VCAN expression in the tumor tissue was higher than that in normal tissue. Elevated expression of VCAN was associated with high the tumor stage and poor long-term survival. There was a significant positive correlation between VCAN and cancer fibroblasts in all pan cancers. Moreover, FBN1 was the intersection gene of VCAN-related genes and linker genes. ANTXR1, COL5A2, CSGALNACT2, and SPARC were the target genes of VCAN genes. GSEA analysis showed that VCAN was mainly enriched in the extracellular matrix (ECM) signaling pathway.CONCLUSION:VCAN can be used as a marker molecule for the early diagnosis of OS and holds significance as a molecule in cases of OS with distant metastasis. The ECM signaling pathway may be a core pathway in OS development and distant metastasis. These findings shed new light on therapeutics of cancers.

目的 基于生物信息学方法筛选并分析晚期骨关节炎(OA)软骨退行性变相关的差异表达基因.方法 选择GSE57218数据集作为分析对象,该数据集是基于GEO公共数据库进行数据检索获得.采用R语言limma工具包筛选DEmRNAs,并对数据进行标准化处理后,利用Metascape在线分析软件及R语言clusterProfiler包分别对DEmRNAs行GO功能和KEGG通路富集分析.选用String在线工具行PPI分析,将结果导入Cytoscape软件得出核心模块与预测核心基因.利用OMIM人类基因数据库筛选出与Hub基因、核心模块的共性表达基因,用GSEA富集分析筛选出核心信号通路及核心基因;将上述筛选出的基因用于预测潜在治疗药物并进行组织定位特异性分析.结果 通过对GSE57218进行分析,共筛选出305个差异表达基因.对上述差异基因行GO和KEGG分析,GO功能富集分析主要富集在NABA核心基质组、ECM的组织、骨骼系统开发、基质组相关、血小板脱粒等.KEGG和GSEA功能富集分析结果显示,与OA发病相关的核心通路为ECM受体相互作用、黏附斑激酶信号通路核心基因.分别对Cytoscape、MCODE、GSEA与OMIM取交集,共筛选出7个靶向基因,PLOD1、COL5A2在平滑肌中特异性表达.结论 筛选出的差异表达基因和相关信号通路有助于理解OA软骨损伤发病的分子机制,同时为临床药物治疗OA的研究提供新思路.

背景:骨膜牵张也具有促进成骨和微血管生成作用,但能否用于治疗糖尿病足目前尚未明确.目的:对骨膜牵张促进骨和血管再生的研究进展进行综述,以明确该技术用于糖尿病足治疗的理论基础,并介绍其在治疗糖尿病足中的初步应用.方法:计算机检索万方医学网、中国知网、PubMed及Elsevier数据库收录的相关文献,中文检索词为:"牵张成组织技术、牵张成骨、胫骨横向骨搬移与糖尿病足、骨膜牵张、骨膜牵张成骨、骨膜牵张与糖尿病足";英文检索词为"Distraction histogenesis,Distraction osteogenesis,Tibia transverse transport and diabetic foot,Periosteal distraction osteogenesis,Periosteal distraction and diabetic foot".最终纳入42篇文献进行综述分析.结果 与结论:①基于Ilizarov张力-应力法则或牵张成组织原理,牵张成骨技术已用于治疗骨缺损、骨不连等疾病,而牵张成骨伴随的成血管原理催生了胫骨横向骨搬移技术,该技术已经成功应用于治疗包括糖尿病足在内的下肢难愈性溃疡,取得良好的治疗效果.②研究发现对骨膜进行持续、稳定、缓慢的牵张可以促进骨和血管再生,即骨膜牵张成骨和成血管现象,该现象的机制可能与骨膜的结构和成分有关.③目前关于骨膜牵张的研究主要聚焦于其成骨功能,且主要停留在动物实验阶段而极少用于人体.与胫骨横向骨搬移促进血管再生从而用于治疗糖尿病足类似,骨膜牵张促进血管再生也可能用于治疗糖尿病足,此即骨膜牵张用于治疗糖尿病足的理论基础.④该课题组已初步将骨膜牵张用于临床治疗糖尿病足,且治疗效果良好,该文章通过展示用于骨膜搬移的器械、手术方法及典型病例.初步结果显示,由于骨膜牵张技术不需要截骨,手术操作要比胫骨横向骨搬移更加简单,手术时间更短;因为骨膜牵张技术缺少对胫骨钻孔和骨搬移的操作,缺乏对胫骨髓腔的"开窗减压"作用及骨组织的搬移,可能促血管生成和创面愈合的效果要弱于胫骨横向骨搬.未来还需对骨膜牵张促进骨和血管再生的具体机制以及手术适应证及禁忌证等进一步研究.

[目的]研究胫骨横向骨搬移(tibia transverse transport,TTT)治疗合并慢性肾病(chronic kidney disease,CKD)的糖尿病足溃疡(diabetic foot ulcer,DFU)的临床疗效.[方法]回顾性分析2015年2月-2019年8月于本科采用TTT治疗的糖尿病足病例资料,其中合并慢性肾病的67例列入肾病组,同期无肾病患者53例,列入无肾病组.比较两组临床与辅助检查结果.[结果]肾病组手术时间、住院时间、拆除外固定时间均大于无肾病组(P＜0.05).随访4～24个月,平均(14.38±4.38)个月.在随访期间肾病组患者有7例患者死亡于心脑血管疾病,无肾病组无患者死亡(P＜0.05).末次随访时两组间足部溃疡愈合率的差异无统计学意义(P＞0.05),但是肾病组溃疡愈合时间显著晚于无肾病组(P＜0.05).至末次随访时,肾病组足部溃疡复发率、截肢率均高于无肾病组,但两组间差异均无统计学意义(P＞0.05).与术前相比,术后两组血管显像均显著改善(P＜0.05);术后1个月时无肾病组的血管显像优于肾病组(P＜0.05),术后3个月时两组间血管显像的差异无统计学意义(P＞0.05).检验方面,与术前相比,术后1个月两组CRP水平、Cr及HbA1c均显著下降(P＜0.05),但Hb,Alb和Urea无显著变化(P＞0.05).相应时间点,肾病组的Hb,Alb显著低于无肾病组(P＜0.05),而Urea、Cr和CRP显著高于无肾病组(P＜0.05).[结论]TTT治疗合并慢性肾病的糖尿病足取得愈合率较高,截肢率、复发率较低的良好效果.

Through the reform of the current postgraduate training mode and the way of mentoring and teaching, such as increasing the proportion of scientific research-related courses, raising the threshold for graduation, establishing a team of tutors to provide effective guidance to students, etc. The idea of forming a postgraduate scientific research team is proposed, and students of different majors and degree types are encouraged to participate in scientific research activities as a team, so as to improve the scientific research atmosphere and scientific research enthusiasm of professional master of clinical medicine (hereinafter referred to as “professional master”), in order to achieve the goal of improving the scientific research and innovation ability of “professional master”, put forward solutions for the problems encountered in the context of the “Double Tracks in One” policy and the large-scale expansion of postgraduate enrollment, and provide theoretical and theoretical ideas for the cultivation of innovation ability of “professional master”. Practical basis.

By reforming the traditional teaching mode, and giving the inspection way, put forward the diversified and “classification guidance” mode of teaching, fully arouse the enthusiasm of students, help trainees to establish scientific research thinking, to achieve the goal of improving the effect of practice and increasing the success rate of postgraduate entrance examination, for the problems existing in the unity of “Double Tracks in One” policy solutions, for further training of high quality medical personnel to improve the basis.

目的 从局部创面毛囊干细胞激活的角度,探讨胫骨横向骨搬移技术促进重度糖尿病足溃疡创面再生、愈合修复的机制.方法 选取2014年6月至2018年1月在广西医科大学第一附属医院骨关节外科行胫骨横向骨搬移的126例重度糖尿病足患者,其中男94例,女32例,年龄39～86岁,中位数年龄61岁.Wagner分级构成:3级67例,4级57例,5级2例;TEXAS分级构成:2B级50例,2C级6例,2D级9例,3B级17例,3C级1例,3D级43例.针对患者进行创面愈合情况临床观察,并在治疗前后取创面边缘组织,进行HE染色观察创面组织学变化,还采用免疫组织化学染色观察富含亮氨酸重复序列的G蛋白偶联受体5(leucine-rich repeat-containing G protein-coupled re-ceptor 5,LGR5)、角蛋白19(cytokeratin 19,CK19)蛋白表达与分布情况.结果 126例重度糖尿病足患者平均愈合时间为(143.5±86.4)d,愈合过程基本呈现炎性期、增殖修复期等阶段特点,即搬移后早期出现创面边缘收缩,表面覆盖较多黄色纤维素样炎性渗出物;换药后逐渐出现鲜红肉芽组织,且边缘上皮组织向中心部位移行增生而基本覆盖创面,仅存线性或条状瘢痕.术后取移行修复创面边缘皮肤组织检测,发现有完整分层结构的表皮,可见大量微血管、胶原纤维和腺体结构,与术前对比,坏死组织减少,真皮有炎细胞浸润减少.治疗后LGR5与和CK19阳性细胞面积比分别为(6.781±1.889)％与(9.095±2.926)％,均显著高于术前创面组织中LGR5和CK19阳性面积比的(1.398±0.620)％与(1.834±0.772)％(P＜0.05).结论 胫骨横向骨搬移技术能促进糖尿病足溃疡创面再生愈合,其机制可能是通过LGR5和CK19等阳性细胞的活化,调控皮肤干细胞,参与创面过程.

Objective To investigate the effectiveness of tibial transverse transport (TTT) combined with nose ring drain (NRD) in the treatment of severe diabetic foot ulcer. Methods The clinical data of 60 patients with severe diabetic foot (Wagner grade 3 or 4) ulcer who were admitted between April 2017 and August 2020 and met the selection criteria were retrospectively analyzed. Among them, 30 cases were treated with TTT combined with NRD (TTT+NRD group), and 30 cases were treated with TTT (TTT group). There was no significant difference in gender, age, diabetes duration, preoperative glycated hemoglobin, comorbidities, wound area, and duration, side, and grade of diabetic foot ( P>0.05). The wound healing time, wound healing rate, amputation rate, recurrence rate, duration of antibiotic therapy, hospital stay, number of hospitalizations, and number of operations were recoreded and compared between the two groups. Results No obvious surgical complications occurred in the two groups. Patients in both groups were followed up 3-13 months, with an average of 5.7 months. The duration of antibiotic therapy and hospital stay in the TTT+NRD group were significantly shorter than those in the TTT group ( P<0.05). There was no significant difference in wound healing time, wound healing rate, number of hospitalizations, and number of operations between the two groups ( P>0.05). During follow-up, there was no recurrence of ulcer in the TTT+NRD group while 2 recurrent cases (6.7%) in the TTT group. The difference in recurrence rate was not significant ( P=0.492). One case (3.3%) in the TTT+NRD group underwent amputation due to acute lower extremity vascular embolism, and 1 case (3.3%) in the TTT group underwent amputation due to secondary necrosis. The difference in amputation rate was not significant between the two groups ( P=1.000). Conclusion TTT combined with NRD is an effective method for the treatment of severe diabetic foot ulcers with deep infections or relatively closed cavities or sinuses. It can shorten the time of antibiotic use and the length of hospitalization; and the NRD has a good drainage effect without obvious comorbidities, procedure and the postoperative care are simple and easy to obtain materials.

The treatment of lower extremity chronic refractory ulcers requires a long time but with poor prognosis. Thus, many patients end up with amputations. The treatment of lower extremity chronic and recalcitrant ulcers and limb salvage has been a challenge worldwide. The Ilizarov technique based on the law of "tension-stress" brings a new hope in treating lower limb chronic and recalcitrant ulcers. The Ilizarov technique and distraction osteogenesis not only induce bone formation but also lead to angiogenesis and improved microcirculation. The Ilizarov technique consists of longitudinal distraction of long bone and tibia trans-verse transport (TTT) (proximal tibial corticotomy followed by transverse distraction). These two techniques have their own advantages and disadvantages with different indications in clinical application. Longitudinal distraction of long bone is mainly used for bone formation, such as large bone defects, osteonecrosis or bone infection (with or without soft tissue loss or ulcers). Because of only a partial osteotomy in TTT, the trauma is minor and their effects on limb instability are limited. Moreover, the procedure is simple with only a few minor complications. Thus, it is ideal in treating lower limb ischemic ulcers, such as diabetic foot ulcers, thromboangiitis obliterans (Buerger's disease), ulcers caused by atherosclerotic occlusion, arterial or venous ulcers, and trauma wounds. Several studies reported that TTT achieved high healing and limb salvage rates in treating severe diabetic foot ulcer. However, TTT could achieve lower recurrent rate. Thus, it is the most successful application in treatment of chronic ulcers. TTT also improves healing and limb salvage in treatment of thromboangiitis obliterans. However, the overall effects are limited than those in treating diabetic foot ulcer. For lower limb atherosclerosis occlusion, TTT induces regeneration of microvessles and consequently leads to ulcer healing. The effects are better than other conventional treatments. A combination therapy with vascularization is emphasized to attain the optimal long-term effects. The effects of TTT on lower limb recalcitrant ulcers still need to be validated in randomized control trial with larger sample size. Further, the mechanism of treatment needs to be explored by pilot studies which could show that this may be related to the formation of pro-angiogenetic factors and a rebalance of the inflammatory microenvironment during TTT.

Objective. The purpose of this study is to identify novel biomarkers for the prognosis of Ewing’s sarcoma based on bioinformatics analysis. Methods. The GSE63157 and GSE17679 datasets contain patient and healthy control microarray data that were downloaded from the Gene Expression Omnibus (GEO) database and analyzed through R language software to obtain differentially expressed genes (DEGs). Firstly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, protein-protein interaction (PPI) networks, and Cytoscape Molecular Complex Detection (MCODE) plug-in were then used to compute the highest scores of the module. After survival analysis, the hub genes were lastly obtained from the two module genes. Results. A total of 1181 DEGs were identified from the two GSEs. Through MCODE and survival analysis, we obtain 53 DEGs from the module and 29 overall survival- (OS-) related genes. ZBTB16 was the only downregulated gene after Venn diagrams. Survival analysis indicates that there was a significant correlation between the high expression of ZBTB16 and the OS of Ewing’s sarcoma (ES), and the low expression group had an unfavorable OS when compared to the high expression group. Conclusions. High expression of ZBTB16 may serve as a predictor biomarker of poor prognosis in ES patients.

Chronic limb ischemic diseases are characterized by symptomatic reduced blood supply to the limbs and can develop into limb-threatening ischemia which is difficult to manage. Distraction osteogenesis induces a large volume of new bone and neovascularization in the surrounding tissues. Consequently, the transverse distraction of tibia has been applied to the management of thromboangiitis obliterans, a chronic limb ischemic disease. However, the application of this technique is still infrequent. Recently, we developed a new technique and coined the term tibial cortex transverse transport (TTT) for it and applied it to severe and recalcitrant diabetic foot ulcers and atherosclerosis obligation and attained excellent clinical outcomes. This review discusses recent advances in the technique of TTT, its application to chronic limb ischemia, the underlying mechanisms, and its potential new clinical applications. The translational potential of this article: TTT has shown promise for the treatment of chronic limb diseases such as diabetic foot ulcer, Buerger’s disease, and arthrosclerosis obliterans in retrospective clinical studies. Its new clinical applications are probably to be extended into the management of other chronic limb diseases such as ulcers of venous, traumatic, embolic, or nonatherosclerotic etiologies, wounds left after tumor resection, radiation, or chemotherapy therapy, or infectious or inflammatory diseases. The surgical procedure is relatively simple and the complications are few and minor. Nevertheless, its effectiveness and safety needs to be confirmed in large population-based trials, and its indications and contraindications are also to be clarified. Additionally, more basic and clinical studies are required to illustrate the underlying mechanisms.

目的:观察胫骨横向骨搬移术治疗下肢血栓闭塞性脉管炎的临床疗效及安全性.方法:2014年2月至2018年9月,采用胫骨横向骨搬移术治疗下肢血栓闭塞性脉管炎患者20例,均为男性.年龄31～56岁,中位数38岁.左侧12例,右侧8例.均有吸烟史,吸烟时间5～33年,中位数21年;吸烟量每日5～60支,中位数35支.均经正规非手术或其他手术治疗无效.均有下肢静息痛和间歇性跛行.下肢单纯溃疡6例,单纯坏疽9例,溃疡和坏疽5例.病程1～7年,中位数3年.记录创面愈合时间,测量跛行距离、足趾皮肤温度及踝肱指数,采用疼痛视觉模拟量表(visual analogue scale,VAS)评分评价患者平卧位休息1 h后患肢静息痛程度,术后随访观察并发症发生情况.结果:所有患者均获随访,随访时间14～69个月,中位数40个月.术后1个月,患者的跛行距离较术前增加[(120±20)m,(1320±531)m,t=10.053,P=0.001]、足趾皮肤温度较术前增高[(28.79±0.58)℃,(32.22±1.01)℃,t=15.188,P=0.001]、踝肱指数较术前增大(0.44±0.03,0.84±0.09,t=23.150,P=0.001)、患肢静息痛VAS评分较术前降低[(5.30±1.78)分,(1.30±1.21)分,t=10.066,P=0.001].20例患者中17例创面愈合,愈合时间(3.6±2.7)个月;3例创面未愈合,其中1例经加强换药后创面最终愈合,1例术后3个月因足部缺血症状加重行小腿中上段截肢术,1例因截骨块感染自行在其他医院摘除骨块后行截肢术.至末次随访时,所有已愈合的溃疡或坏疽均未复发,均未出现胫骨骨折、钉道感染、截骨块延迟愈合、下肢深静脉血栓等并发症.结论:胫骨横向骨搬移术治疗下肢血栓闭塞性脉管炎,可以减轻患肢疼痛症状、增加跛行距离、提高足趾皮肤温度及踝肱指数,有利于创面愈合,且安全性较高.

OBJECTIVE:The treatment of recalcitrant not-diabetic leg ulcers remains challenging. Distraction osteogenesis is accompanying by angiogenesis and neovascularization in the surrounding tissues. We previously applied tibial cortex transverse transport (TTT) to patients with recalcitrant diabetic foot ulcers and found neovascularization and increased perfusion in the foot and consequently enhanced healing and limb salvage and reduced recurrence. However, the effects of TTT on recalcitrant non-diabetic leg ulcer remains largely unknown. METHODS:Consecutive patients (n ​= ​85) with recalcitrant non-diabetic leg ulcers (University of Texas Grade 2-B to 3-D, ie, wound penetrating to the tendon, capsule, bone, or joint with infection and/or ischemia) were recruited and divided into TTT (n ​= ​42) and control (n ​= ​43) groups based on the treatment they received. There were 36 (85.7%) arterial ulcers, 4 (9.5%) venous ulcers and 2 (4.8%) mixed ulcers in the TTT group and 32 (74.4%) arterial ulcers, 7 (16.7%) venous ulcers and 4 (9.3%) mixed ulcers in the control group (p ​> ​0.05). The two groups were matched on demographic and clinical characteristics. Patients in the TTT group underwent tibial corticotomy followed by 4 weeks of distraction medially then laterally, while those in the control group received conventional surgeries (debridements, revascularization, reconstruction with flaps, or skin grafts or equivalents). Ulcer healing and healing time, limb salvage, recurrence, and patient death were evaluated at a 1-year follow-up. Changes in leg small vessels were assessed in the TTT group using computed tomography angiography (CTA). RESULTS:TTT group had higher healing rates at 1-year follow-up than the control group (78.6% [33/42] vs. 58.1% [25/43], OR 2.64 [95% CI 1.10 to 6.85], p ​= ​0.04). The healing time of the TTT group was shorter than the control group (4.5 vs. 6.1 months, mean difference -1.60 [95% CI -2.93 to -0.26], p ​= ​0.02). There were no significant differences in rates of major amputation, reulceration, or mortality between the groups (p ​> ​0.05). TTT group displayed more small vessels 4 weeks postoperatively at the wound area, the foot, and the calf of the ipsilateral side in CTA. All patients in the TTT group achieved good union at the osteotomy site and had no skin or soft tissue necrosis or infection around the incision area. CONCLUSION:The findings showed that TTT facilitated the healing of recalcitrant non-diabetic leg ulcers and reduced the healing time compared with conventional surgeries. They suggest that TTT is an effective procedure to treat recalcitrant non-diabetic foot ulcers compared with standard surgical therapy. The procedure of TTT is relatively simple. Randomized controlled trials are required to confirm these findings. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE:TTT can be used as an effective treatment for recalcitrant non-diabetic leg ulcers in patients. The mechanism may be associated with the neovascularization in the ulcerated foot induced by TTT and consequently increased perfusion. Together with previous findings from recalcitrant diabetic leg ulcers, the findings suggest TTT as an effective procedure to treat recalcitrant chronic leg ulcers.

目的:探讨重度糖尿病足胫骨横向骨搬移术治疗后创面愈合方式及机制.方法:2014年12月至2018年6月收治136例重度糖尿病足患者.按照Wagner分级标准,3级66例、4级60例、5级10例.按照TEXAS分级标准,2B级32例、2C级2例、2D级11例、3B级13例、3D级78例.均采用胫骨横向骨搬移术治疗.对创面愈合过程进行大体观察,同时分别于术前及术后1个月复诊时切取创面边缘组织,HE染色观察创面组织形态,免疫组织化学染色观察Ki-67、CD31和血管内皮生长因子(vascular en-dothelial growth factor,VEGF)表达情况.结果:①创面大体观察结果.术后初期创面处于炎性期,有炎性细胞浸润,创面黄白;随后有新鲜肉芽组织形成,肉芽组织由创面周围向创面中心移行,创面红润,进入增生期;肉芽组织覆盖创面的过程中,上皮组织逐渐由创面四周向中心移行,1～3个月时创面愈合50%左右,上皮组织最终覆盖创面,仅留线性瘢痕.②创面组织形态观察结果.术前创面边缘组织表皮结构不完整,坏死结构较多.术后1个月创面边缘组织可清晰地观察到完整表皮结构,分为角质层、颗粒层、棘层和基底层;真皮层结缔组织中可观察到血管及胶原纤维,纤维结构少见.术前、术后创面边缘组织表皮均有大量炎性细胞浸润.③术后1个月时,创面边缘组织中 Ki -67、CD31、VEGF染色阳性细胞面积百分比均大于术前[(1.850 ± 1.287)%, (7.480 ± 5.272)%,Z＝3.292,P＝0.001;(0.395 ± 0.139)%,(1.082 ± 0.636)%,Z＝3.403,P＝0.001;(0.341 ± 0.217)%,(2.428 ± 1.502)%,Z＝3.780,P＝0.000].结论:胫骨横向骨搬移术能有效促进重度糖尿病足创面愈合,治疗后创面愈合方式为再生愈合,其机制可能是该手术能促进创面组织细胞增殖与毛细血管再生.