BACKGROUND:We report orthotopic combined whole-liver and bilateral-kidney xenotransplantation (xeno-CLKT) from a six-gene-edited pig into a 53-year-old human decedent recipient. METHODS:After simultaneous implantation and reperfusion, graft function was monitored for nearly 5 days using continuous clinical assessments. Host responses were further characterized with single-cell RNA sequencing, proteomics, and metabolomics of blood and graft tissues collected before and after transplantation. FINDINGS:All grafts maintained basic physiological function throughout the observation period, with no evidence of hyperacute rejection. Early post-transplant immune analysis showed expansion of S100A12+ neutrophils, which emerged as central hubs in inferred intercellular communication networks. Systems-level metabolomic profiling indicated that post-transplant metabolic patterns remained positively correlated with the recipient's pre-transplant baseline, with generally higher magnitudes. CONCLUSIONS:This study provides initial evidence for the feasibility of pig-to-human orthotopic whole-liver plus bilateral-kidney transplantation and identifies early immune and metabolic features that may inform perioperative management and future clinical translation. FUNDING:The research was supported by the Guangxi Key Research and Development Program (AB24010059), the Shenzhen Medical Research Fund (SMAF) (B2302008), and the Guangdong Province Guangdong-Shenzhen Joint Key Project (2023B1515120083).

Intraportal islet transplantation for treating insulin-dependent diabetes mellitus has been clinically validated. However, the hypoxic environment and sinusoidal architecture of the liver are unsuitable for the long-term survival of transplanted islets, leading to the loss of therapeutic effects within a year. The spleen has oxygen levels that meet islet needs, but intense instant blood-mediated inflammatory reactions (IBMIR) and low extracellular matrix (ECM) concentrations hinder islet engraftment and survival. In this study, we developed constructs of islets encapsulated by hepatocytes and fibroblasts. The hepatocytes and fibroblasts create a protective coating that reduces IBMIR due to the low expression of von Willebrand factor (vWF) in hepatocytes and supports normal islet survival through ECM production by fibroblasts. These constructs can be easily injected into the mouse spleen. The hepatocyte-fibroblast encapsulation significantly reduces islet mortality during the post-transplantation stress period, enabling rapid engraftment and vascularization in the spleen. The spleen's high-oxygen environment then supports long-term (over one year) islet survival and sustained glycemic regulation. Additionally, this method significantly lowers the critical islet dose required for transplantation. The live-cell shielding strategy developed in this study represents a novel approach for islet transplantation and functional regeneration, demonstrating promising clinical potential.

Tibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT. We established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes. The TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity. Our innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.

BACKGROUND:Diabetes mellitus (DM) can cause severe complications, including diabetic foot ulcers (DFU). There is a significant gap in understanding the single-cell ecological atlas of DM and DFU tissues. METHODS:Single-cell RNA sequencing data were used to create a detailed single-cell ecological landscape of DM and DFU. Enrichment analysis identified pathways involved in cellular subpopulations, and pseudo-time analysis inferred cell development processes. A gene regulatory network explored the role of transcription factors in DFU progression, and a potential herbal drug-target gene interaction network was constructed. RESULTS:In the DFU group, immune cells were activated, with notable changes in several subpopulations. ATP5E was significantly overexpressed in Naive T cells, fibroblasts, endothelial cells, and CD8+ T cells in DM patients. Specific immune cell subsets, such as Naive T_RGCC, CTL_TYROBP_CL4, Mac_SLC40A1, and M1_CCL3L1, likely contribute to DFU formation through overactivation and proliferation, leading to tissue damage and ulcer exacerbation. Key genes TPP1, TLR4, and RIPK2 were identified, and 88 active ingredients in the herbal drug-target network showed strong correlations with these targets. Herbs like Angelica dahurica, Angelica sinensis, Boswellia carterii, liquorice, myrrh, and Semen armeniacae amarae were included. CONCLUSIONS:This study offers insights into DM and DFU cytology. T cells in DFU are activated, attacking normal tissues and worsening tissue damage. The ATP5E gene may be related to the ecological remodeling of DM, and TPP1, TLR4, and RIPK2 are potential targets for DFU treatment.

Objective: The clinical management of patients with chronic limb-threatening ischemia (CLTI) faces great challenges. Enhancing wound healing and limb preservation rates in this cohort is a critical objective. This study investigates the effectiveness of combining tibial cortex transverse transport (TTT) and endovascular therapy (EVT) for the treatment of patients with severe CLTI. We aim to evaluate the therapeutic results of this combined approach on the specified patient group. Methods: We conducted a retrospective study to compare EVT with the combination of TTT and EVT in patients (Rutherford category 5 and above) with CLTI at Guangxi Medical University's First Affiliated Hospital from June 2017 to June 2023. This cohort was subjected to a follow-up period ranging from a minimum of 6 months to a maximum of 12 months. The primary outcome measures included amputation-free survival (AFS) (avoidance of above-ankle amputation or death from any cause), overall mortality, limb salvage rates, wound healing efficiency, and the technical efficacy of the applied treatments. A variety of statistical analyses including chi-square tests, Fisher's exact tests, and Pearson's and Spearman's correlation analyses. Results: In this study, 131 patients with CLTI were included: 76 in the control group receiving only EVT treatment and 55 in the TTT + EVT group. The two groups were matched on demographic and clinical characteristics. In the TTT + EVT group, after more than 6 months of follow-up, 85.5% of patients achieved AFS, and wound healing was observed in 54.5% (30 of 55 patients). After more than 12 months of follow-up, 81.9% achieved AFS, with wound healing in 32 patients. Furthermore, after more than 24 months, 74.2% of patients remained amputation-free, with wound healing in all surviving patients. In the control group, after more than 6 months of follow-up, 72.4% of patients achieved AFS, and wound healing was observed in 51.3% (39 of 96 patients). After more than 12 months, 48.9% achieved AFS, with wound healing in 21 patients. Conclusion: We found that combining therapy of TTT and EVT is safe and can be successfully administered in patients with CLTI and it enhances wound healing and AFS.

Purpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration. Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1 alpha, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA. Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31(+) cells (all p < 0.001) and VEGFR2(+) cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1 alpha, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1 alpha, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001). Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1 alpha-induced angiogenesis.

The shortage of liver grafts is still an unsolved challenge for the transplantation community, and the development of new approaches for liver preservation and reconditioning is urgently needed. Machine perfusion techniques hold great promise for increasing the number of donor livers and reducing post-transplantation complications. These techniques can not only preserve donor livers, but also repair and maintain liver function of marginal donors.1Eden J Sousa Da Silva R Cortes-Cerisuelo M et al.Utilization of livers donated after circulatory death for transplantation—an international comparison.J Hepatol. 2023; 78: 1007-1016Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Despite these advancements, many liver grafts fail to meet the viability test thresholds required for transplantation. Improved perfusion devices are therefore required to extend the perfusion duration for assessing, recovering, and modifying marginal livers before transplantation. This highlights new methods for ameliorating donor organ shortages and permitting targeted therapies.2Eshmuminov D Becker D Bautista Borrego L et al.An integrated perfusion machine preserves injured human livers for 1 week.Nat Biotechnol. 2020; 38: 189-198Crossref PubMed Scopus (197) Google Scholar, 3Clavien PA Dutkowski P Mueller M et al.Transplantation of a human liver following 3 days of ex situ normothermic preservation.Nat Biotechnol. 2022; 40: 1610-1616Crossref PubMed Scopus (53) Google Scholar To preserve the metabolic activity of the liver during long-term perfusion, the devices must mimic the human body to maintain the organ's physiological environment through integrating multiple core functions. However, device optimisation processes and viability test approvals take a long time. Various additional therapeutics to repair and regenerate marginal livers are currently being tested, such as defatting cocktails, cell-based therapies, genetic modulation, senolytics, and functional liver scaffolds.4Schlegel A Mergental H Fondevila C Porte RJ Friend PJ Dutkowski P Machine perfusion of the liver and bioengineering.J Hepatol. 2023; 78: 1181-1198Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Despite many innovative bioengineering technologies being developed, most that can be combined with machine perfusion are still flawed and in their infancy. Extensive clinical trials are also required before their use in clinical practice. In addition to clinical benefits, economic benefits need to be considered in fully establishing and implementing new technologies. We declare no competing interests. This Correspondence was funded by the National Natural Science Foundation of China (81670596; awarded to XS) and the High-Level Medical Expert Training Program of Guangxi “139” Plan Funding (G202002016; awarded to XS).

Background: Tibial Cortex Transverse Transport (TTT) has been demonstrated to be an effective treatment for unilateral diabetic foot ulcers (UDFUs). However, this retrospective study was designed to compare the efficacy and safety of unilateral TTT on bilateral diabetic foot ulcers (BDFUs).Methods: This retrospective study included a review of patients with TTT treated from January 2017 to August 2019, Propensity Score Matching (PSM) was performed to compare patients with BDFUs to those with UDFUs. Ulcer healing, recurrence, and major amputation rates were evaluated at 1-year follow-up. Changes in foot vessels were assessed in the BDFUs group using computed tomography angiography (CTA).Results: A total of 140 patients with DFUs (106 UDFUs and 34 BDFUs) were included in the study. UDFUs and BDFUs were matched in a 1:1 ratio (34 in each group) using PSM. No significant difference was observed at 1 -year-follow-up [91.2% (31/34) vs. 76.5% (26/34), OR 0.315 (95% CI 0.08 to 1.31), P = 0.10] and 6-month -follow-up [70.6% (24/34) vs. 50.0% (17/34), OR 0.85 (95% CI 0.15 to 1.13), P = 0.08] in two groups. Signif-icant differences in rates of major amputation and recurrence between the groups (P > 0.05) were not observed. The BDFUs group appeared more angiogenesis of the foot by CTA after 8 weeks of operation.Conclusion: Results of this study suggest that severe BDFUs can be effectively treated by unilateral TTT. TTT is easy to operate and effective, which may be a good alternative for treating severe BDFUs. The translational potential of this article: In previous retrospective clinical studies, TTT has demonstrated promising clinical outcomes in the management of diabetic foot ulcers. In this current study, we aim to investigate the potential use of TTT in treating distant tissue defects by evaluating the limited availability and safety of TTT for the management of bilateral diabetic foot. While additional basic and clinical research is necessary to fully elucidate the underlying mechanisms, our study offers insight into the potential therapeutic use of TTT for this condition.

目的 探讨胫骨横向骨搬移术(TTT)促进重度糖尿病足创面愈合的作用机制.方法 选择重度糖尿病足患者61例,观察手术前后创面愈合情况.受经费及患者依从性限制,分别随机挑选Wagner分级3级、4级、5级各4例患者,于术前及术后1个月对其创面边缘愈合组织行免疫组化检测,并观察手术前后CD86、CD163、CD31、血管内皮生长因子(VEGF)阳性细胞计数变化,以CD86、CD163单克隆抗体分别标记M1、M2型巨噬细胞,应用Image Pro Plus 6.0软件统计阳性细胞数,计算M1/M2值,并观察术前、术后1个月创面边缘组织HE染色情况.术前、术后1个月行足部血管造影检查观察足部血管变化.结果 61例患者创面全部愈合,愈合时间1～12(3.83±2.31)个月,创面愈合过程基本按炎症期、增殖期和重塑期3个阶段发展.免疫组化结果显示,术后1个月,CD86、CD163阳性细胞较术前减少,VEGF、CD31阳性细胞较术前增加;术后1个月M1、M2型巨噬细胞计数较术前减少,M1/M2较术前降低(均P＜0.05).术前HE染色发现组织残缺,未见皮肤附属器,术后新生皮肤组织结构完整,可见腺体样结构和胶原沉积.足部血管造影检查发现术前微血管少,术后微血管增多.结论 TTT可显著促进重度糖尿病足创面再生愈合,可能与降低巨噬细胞M1/M2值,抑制创面炎症,促进微血管再生增多有关.

Background:Management of recalcitrant diabetic foot ulcer (DFU) remains difficult. Distraction osteogenesis mediates new bone formation and angiogenesis in the bone itself and the surrounding tissues. Recently it was reported that tibial cortex transverse transport (TTT) was associated with neovascularization and increased perfusion at the foot in patients with recalcitrant DFUs and facilitated healing and limb salvage. However, the findings were from several single-center studies with relatively small populations, which need to be confirmed in multicenter cohort studies with relatively large populations. Furthermore, the effect of this technique on patient's health-related quality of life is still unclear. Methods:We treated patients with recalcitrant (University of Texas wound grading system 2-C to 3-D and not responding to prior routine conservative and surgical treatments for at least 8 weeks) DFUs from seven centers using TTT (a 5 ​cm ​× ​1.5 ​cm corticotomy followed by 4 weeks of medial and lateral distraction) between July 2016 and June 2019. We analyzed ulcer healing, major amputation, recurrence, health-related quality of life (physical and mental component summary scores), and complications in the 2-year follow-up. Foot arterial and perfusion changes were evaluated using computed tomography angiography and perfusion imaging 12 weeks postoperatively. Results:A total of 1175 patients were enrolled. Patients who died (85, 7.2%) or lost to follow-up (18, 1.7%) were excluded, leaving 1072 patients for evaluation. Most of the patients were male (752, 70.1%) and with a mean age of 60.4 ​± ​9.1 years. The mean ulcer size was 41.0 ​± ​8.5 ​cm2 and 187 (16.6%) ulcers extended above the ankle. During the follow-up, 1019 (94.9%) patients healed in a mean time of 12.4 ​± ​5.6 weeks, 53 (4.9%) had major amputations, and 33 (3.1%) experienced recurrences. Compared to preoperatively, the patients had higher physical (26.2 ​± ​8.3 versus 41.3 ​± ​10.6, p ​= ​0.008) and mental (33.6 ​± ​10.7 versus 45.4 ​± ​11.3, p ​= ​0.031) component summary scores at the 2-year follow-up. Closed tibial fracture at the corticotomy site was found in 8 (0.7%) patients and was treated using external fixation and healed uneventfully. There were 23 (2.1%) patients who had pin site infections and were treated successfully with dressing changes. Compared to preoperatively, the patients had more small arteries and higher foot blood flow (8.1 ​± ​2.2 versus 28.3 ​± ​3.9 ml/100 ​g/min, p ​= ​0.003) and volume (1.5 ​± ​0.3 versus 2.7 ​± ​0.4 ml/100 ​g, p ​= ​0.037) 12 weeks postoperatively. Conclusion:TTT promotes healing, limb salvage, and health-related quality of life in patients with recalcitrant DFUs as demonstrated in this multicenter cohort study. The surgical procedure was simple and straightforward and the complications were few and minor. The effect of this technique was associated with neovascularization and improved perfusion at the foot mediated by the cortex distraction. The findings are required to confirm in randomized controlled trials.The Translational Potential of this Article: TTT can be used as an effective treatment in patients with recalcitrant DFUs. The mechanism is associated with neovascularization and consequently increased perfusion in the foot after operation.

目的:探讨腓骨横向骨搬移术治疗重度糖尿病足的疗效和安全性,并与胫骨横向骨搬移术治疗重度糖尿病足对比.方法:回顾性分析2016年8月至2021年10月接受治疗的重度糖尿病足患者30例,将患者按随机数字表法分为腓骨横向骨搬移组、胫骨横向骨搬移组和传统治疗组3组,每组10例,术后观察患者足部溃疡愈合情况,评估住院时间、疼痛评分症状等,并计算愈合率、保肢率、复发率等情况.结果:所有患者均获得随访,随访时间5～48个月,平均(19.1±2.3)个月.腓骨横向骨搬移组患者患足9例愈合,愈合率90.0％,创面平均愈合时间(15.4±4.3)周,全部保肢,保肢率100％;且患者治疗后的疼痛、麻木症状均得到显著改善.至末次随访时,所有已愈合的溃疡均未复发.腓骨横向骨搬移组、胫骨横向骨搬移组溃疡复发率和患者截肢率均优于传统治疗组(均P＜0.05).结论:腓骨横向骨搬移术对糖尿病足有较好的临床疗效,能加速创面愈合,有效降低患者糖尿病足坏死截肢率.

BackgroundOsteoblasts-Osteoclasts has been a major area in bone disease research for a long time. However, there are few systematic studies in this field using bibliometric analysis. We aimed to perform a bibliometric analysis and visualization study to determine hotspots and trends of osteoblasts-osteoclasts in bone diseases, identify collaboration and influence among authors, countries, institutions, and journals, and assess the knowledge base to develop basic and clinical research in the future.MethodsWe collected articles and reviews for osteoblasts-osteoclasts in bone diseases from the Web of Science Core Collection. In addition, we utilized scientometrics software (CiteSpace5.8 and VOSviewer1.6.18) for visual analysis of countries/regions, institutions, authors, references, and keywords in the field.ResultsIn total, 16,832 authors from 579 institutions in 73 countries/regions have published 3,490 papers in 928 academic journals. The literature in this field is rapidly increasing, with Bone publishing the most articles, whereas Journal of Bone and Mineral Research had the most co-cited journals. These two journals mainly focused on molecular biology and the clinical medicine domain. The countries with the highest number of publications were the US and China, and the University of Arkansas for Medical Sciences was the most active institution. Regarding authors, Stavros C. Manolagas published the most articles, and Hiroshi Takayanagi had the most co-cited papers. Research in this field mainly includes molecular expression and regulatory mechanisms, differentiation, osteoprotection, inflammation, and tumors. The latest research hotspots are oxidative stress, mutation, osteocyte formation and absorption, bone metabolism, tumor therapy, and in-depth mechanisms.ConclusionWe identified the research hotspots and development process of osteoblasts-osteoclasts in bone disease using bibliometric and visual methods. Osteoblasts-osteoclasts have attracted increasing attention in bone disease. This study will provide a valuable reference for researchers concerned with osteoblasts-osteoclasts in bone diseases.

[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.

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.

Tibial transverse transport (TTT) was firstly applied to treat thromboangiitis obliterans successfully by Professor QU Long in China in 2000. Based on this, the team of Professor HUA Qikai in the First Affiliated Hospital of Guangxi Medical University applied this technique to treat diabetic foot since 2013, and until now, more than 500 patients underwent this treatment with excellent effectiveness including a salvage rate as high as 96.1%. Our team also improved this technique in many aspects, and developed a TTT-based classification system and treatment for diabetic foot. We also explored the underlying mechanism of TTT treatment using imaging, histology, and other basic research methods. To further promote the application of this technique in clinic, we reported the findings from our cases and reviewed our previous findings in this study.

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.