Acute rejection is a life-threatening complication after liver transplantation. Immunosuppressants such as tacrolimus are used to inhibit acute rejection of liver grafts in clinic. However, inefficient intragraft accumulation may reduce the therapeutic outcomes of tacrolimus. Here, an enzyme-responsive nanoparticle is developed to selectively enhance the accumulation of tacrolimus in liver allograft through enzyme-induced aggregation to refine immunotherapeutic efficacy of tacrolimus. The nanoparticles are composed of amphiphilic tacrolimus prodrugs synthesized by covalently conjugating tacrolimus and matrix metalloproteinase 9 (MMP9)-cleavable peptide-containing methoxy poly (ethylene glycol) to poly (l-glutamic acid). Upon exposure to MMP9, which is overexpressed in rejected liver allografts, the nanoparticles undergo a morphological transition from spherical micellar nanoparticles to microscale aggregate-like scaffolds. Intravenous administration of MMP9-responsive nanoparticles into a rat model of acute liver graft rejection results in enhanced nanoparticle accumulation in allograft as compared to nonresponsive nanoparticles. Consequently, the MMP9-responsive nanoparticles significantly inhibit intragraft inflammatory cell infiltration and proliferation, maintain intragraft immunosuppressive environment, alleviate graft damage, improve liver allograft function, abate weight loss and prolong recipient survival. This work proves that morphology-switchable enzyme-responsive nanoparticles represent an innovative strategy for selectively enhancing intragraft accumulation of immunosuppressive agents to improve treatment of liver allograft rejection.

OBJECTIVES: Tracheal reconstruction post-extensive resection remains an unresolved challenge in thoracic surgery. This study evaluates the use of aortic allografts (AAs) for tracheal replacement and reconstruction in a rat model, aiming to elucidate the underlying mechanisms of tracheal regeneration. METHODS: AAs from female rats were employed for tracheal reconstruction in 36 male rats, with the replacement exceeding half of the tracheal length. To avert collapse, silicone stents were inserted into the AA lumens. No immunosuppressive therapy was administered. The rats were euthanized biweekly, and the AAs were examined for neovascularization, cartilage formation, respiratory epithelial ingrowth, submucosal gland regeneration and the presence of the Sex-determining region of Y-chromosome (SRY) gene. RESULTS: All procedures were successfully completed without severe complications. The AA segments were effectively integrated into the tracheal framework, with seamless distinction at suture lines. Histological analysis indicated an initial inflammatory response, followed by the development of squamous and mucociliary epithelia, new cartilage ring formation and gland regeneration. In situ hybridization identified the presence of the SRY gene in newly formed cartilage rings, confirming that regeneration was driven by recipient cells. CONCLUSIONS: This study demonstrates the feasibility of AAs transforming into functional tracheal conduits, replicating the main structural and functional characteristics of the native trachea. The findings indicate that this approach offers a novel pathway for tissue regeneration and holds potential for treating extensive tracheal injuries.

AbstractRestoration of extensive tracheal damage remains a significant challenge in respiratory medicine, particularly in instances stemming from conditions like infection, congenital anomalies, or stenosis. The trachea, an essential element of the lower respiratory tract, constitutes a fibrocartilaginous tube spanning approximately 10–12 cm in length. It is characterized by 18 ± 2 tracheal cartilages distributed anterolaterally with the dynamic trachealis muscle located posteriorly. While tracheotomy is a common approach for patients with short‐length defects, situations requiring replacement arise when the extent of lesion exceeds 1/2 of the length in adults (or 1/3 in children). Tissue engineering (TE) holds promise in developing biocompatible airway grafts for addressing challenges in tracheal regeneration. Despite the potential, the extensive clinical application of tissue‐engineered tracheal substitutes encounters obstacles, including insufficient revascularization, inadequate re‐epithelialization, suboptimal mechanical properties, and insufficient durability. These limitations have led to limited success in implementing tissue‐engineered tracheal implants in clinical settings. This review provides a comprehensive exploration of historical attempts and lessons learned in the field of tracheal TE, contextualizing the clinical prerequisites and vital criteria for effective tracheal grafts. The manufacturing approaches employed in TE, along with the clinical application of both tissue‐engineered and non‐tissue‐engineered approaches for tracheal reconstruction, are discussed in detail. By offering a holistic view on TE substitutes and their implications for the clinical management of long‐segment tracheal lesions, this review aims to contribute to the understanding and advancement of strategies in this critical area of respiratory medicine.

The liver is an important organ in the human body and performs many functions, such as digestion, detoxification, metabolism, immune responses, and vitamin and mineral storage. Therefore, disorders of liver functions triggered by various hepatic diseases, including hepatitis B virus infection, nonalcoholic steatohepatitis, hepatic fibrosis, hepatocellular carcinoma, and transplant rejection, significantly threaten human health worldwide. Polymer-based nanomedicines, which can be easily engineered with ideal physicochemical characteristics and functions, have considerable merits, including contributions to improved therapeutic outcomes and reduced adverse effects of drugs, in the treatment of hepatic diseases compared to traditional therapeutic agents. This review describes liver anatomy and function, and liver targeting strategies, hepatic disease treatment applications and intrahepatic fates of polymeric nanomedicines. The challenges and outlooks of hepatic disease treatment with polymeric nanomedicines are also discussed.

Objective. Thrombocytopenia is a common condition in patients undergoing liver transplantation (LT). Thrombocytopenia is prevalent in early postoperative phase, and it gradually improves after several weeks. Delayed severe thrombocytopenia occurring after the initial recovery of platelets is rare. We report a case of a patient with delayed severe thrombocytopenia 59 weeks after LT. Case Presentation. Our patient was a 61-year-old man who presented to our institution 59 weeks after undergoing LT. He presented for removal of a bile duct stent that was inserted 3 months prior. Tacrolimus replaced sirolimus for immunosuppression during the seventh week after transplantation due to sirolimus-induced nephrotoxicity. On admission, the patient's vital signs were normal and his physical examination was unremarkable. Laboratory parameters demonstrated that the platelet (PLT) level was significantly decreased to 18 x 10(9)/L. PLTs reached a nadir of 3 x 10(9)/L even after utilization of interleukin-11, thrombopoietin, and low-dose prednisone. Although rare, sirolimus toxicity was suspected. Therefore, sirolimus was gradually replaced by cyclosporin A in combination with low-dose prednisone. Subsequently, a normal PLT level was gradually recovered. This study was approved by the ethical committee of the First Hospital of Jilin University and was performed in accordance with the ethical standards of the Helsinki Congress and Istanbul Declaration. Conclusions. Recurrent delayed severe thrombocytopenia is rare after LT. Sirolimus toxicity might be a reason for its occurrence if other possible factors are excluded. After diagnosis, sirolimus therapy should be discontinued and patients should be treated with an alternative immunosuppressive regimen.

Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction is a common and preferred choice for gallstone disease. Laparoscopic common bile duct exploration (LCBDE) and laparoscopic cholecystectomy (LC) are being increasingly used for managing choledocholithiasis and cholecystolithiasis. We report a case of a Hem-o-lok clip that was dropped into the common bile duct (CBD) after LC and surgical common bile duct exploration (CBDE). An 84-year-old man presented with right upper quadrant pain and jaundice for 2 months, and chills and hyperpyrexia for 1 day. The patient had received ERCP and surgical CBDE at a local hospital 3 years previously. The patient first received ERCP and endoscopic nasobiliary drainage (ENBD). When laboratory tests were normal, the patient then received LCBDE. During exploration, stones and a Hem-o-lok clip in the CBD were removed. The patient made good progress after LCBDE + T-tube placement and was discharged from hospital. The findings from this case suggest the following: 1) an appropriate therapy method should be considered for certain gallstone diseases, especially for choledocholithiasis and cholecystolithiasis; and 2) a Hem-o-lok clip should be carefully used during laparoscopic or robot-assisted surgery and the Hem-o-lok clip should not be in close proximity to the incision on the CBD.

胆管消失综合征较为少见，无明显临床特征，诊断依赖于肝穿刺活检。发病早期可通过口服熊去氧胆酸缓解，但多有复发。晚期可出现胆汁淤积性肝硬化，甚至肝衰竭，肝移植是唯一有效治疗方案。本文报道了我中心1例胆管消失综合征女性患者，行肝移植治疗，临床效果明确，目前已存活18个月。

Objective To analyze the risk factors of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC),and to establish a preoperative prediction model for MVI.Methods The clinical data of 159 patients with HCC from the First Hospital of Jilin University treated from January 2012 to December 2014 were retrospectively analyzed.There were 128 males and 31 females.Univariate and multivariate logistic regression analysis of factors influencing the presence of MVI in HCC patients were carried out.Independent risk factors were scored based on the β values of multivariate analysis.Receiver operating characteristics (ROC) curves were used to evaluate the predictive value of the scores for the risk factor for MVI.Results Univariate and multivariate logistic regression analyses showed that age ≥ 60 years (OR=0.263,95％ CI:0.112 ～ 0.614),tumor diameter ≥5 cm (OR=3.902,95％ CI:1.784 ～ 8.583),neutrophil to lymphocyte ratio (NLR) ≥ 1.83 (OR=2.414,95％ CI:1.065～5.472) and platelet to lymphocyte ratio (PLR) ≥ 72.30 (OR =2.578,95％ CI:1.068～ 6.223) were the influencing factors of MVI in patients with HCC (P＜0.05).The preoperative prediction model of MVI was established using the MVI independent risk factor scores.The area under the ROC curve was 0.793 (95％ CI:0.723～ 0.862).The optimal cutoff value for the presence of MVI was 2.75 points,and the sensitivity was 0.72 and the specificity was 0.78.The MVI positive rates of patients with risk scores of 0 to 1.5,2.0 to 3.5,and 4.0 to 5.0 were 18.6％,42.9％,and 78.3％,respectively.Conclusion Age,tumor diameter,NLR,and PLR were independent factors influencing MVI in patients with HCC.The preoperative model based on the independent risk factor scores can be used to predict the presence of MVI in HCC patients.

肝内胆管囊腺癌是一种临床少见的肝脏恶性肿瘤,目前病因尚不明确,其起病隐匿,病程较长,主要有右上腹不适、疼痛、右上腹包块、肝肿大及体重减轻等症状.由于肝内胆管囊腺癌无特异临床表现,加之缺乏有效的辅助检查手段,同时该病与胆管内乳头状黏液性瘤(intraductal papillary muc-inousneoplasm of the bile duct,IPMN-B)、肝内胆管囊腺瘤的临床表现、辅助检查极其相似,临床上对三者的鉴别诊断存在很大的困难.本文通过总结近年来国内外相关文献,对肝内胆管囊腺癌的诊治特点做一阐述,旨在提高外科医师对该病的认识,减少漏诊及误诊,使患者获得良好的预后与生存质量.

目的 探讨单发肝细胞癌(SHCC)发生微血管侵犯的影响因素及患者预后情况.方法 回顾性分析2012年1月-2014年12月吉林大学第一医院收治的138例行肝癌根治术SHCC患者的临床病理资料.根据中性粒细胞、PLT、纤维蛋白原、中性粒细胞与淋巴细胞比值、PLT与淋巴细胞比值、纤维蛋白原与Alb比值和是否发生微血管侵犯绘制受试者工作特征曲线,依据约登指数确定各指标的临界值.应用logistic回归模型行单因素和多因素分析,比值比(0R)和95％可信区间(95％CI)评价联系的紧密性.对微血管侵犯阳性与阴性患者应用Kaplan-Meier法计算无瘤生存率,并绘制生存曲线,采用log-rank检验进行比较.结果 单因素分析显示,与SHCC微血管侵犯相关的因素有性别(OR =0.400,95％CI:0.162 ～0.985,P=0.046)、肿瘤直径(OR=5.902,95％CI:2.813 ～12.382,P＜0.001)、AFP(OR =2.635,95％ CI:1.286 ～5.398,P=0.008)、中性粒细胞(OR =3.019,95％CI:1.353～6.736,P=0.007)、PLT(OR=2.255,95％CI:1.116～4.555,P=0.023)、纤维蛋白原(OR=3.483,95％CI:1.687 ～7.190,P=0.00l)、GGT(OR=2.115,95％CI:1.069 ～4.182,P=0.031)、中性粒细胞与淋巴细胞比值(OR=3.662,95％CI:1.803 ～7.436,P＜0.001)、PLT与淋巴细胞比值(OR=3.734,95％CI:1.649 ～ 8.455,P=0.002)、纤维蛋白原与Alb比值(OR=3.014,95％CI:1.497～6.070,P=0.002).多因素分析显示,肿瘤直径(OR=5.423,95％CI:2.555 ～11.511,P＜0.001)和AFP(OR =2.195,95％CI:1.010 ～4.774,P=0.047)是微血管侵犯的独立相关因素.预后研究结果表明,有微血管侵犯组患者l、3年无瘤生存率为66.4％、52.8％,无微血管侵犯组患者l、3年无瘤生存率为90.6％、71.5％,2组患者1、3年无瘤生存率比较差异有统计学意义(x2值分别为10.929、4.043,P值均＜0.05).2组无瘤生存曲线比较,差异亦有统计学意义(x2=7.860,P=0.005).结论 肿瘤直径、术前AFP水平是SHCC发生微血管侵犯的独立相关因素,SHCC伴有微血管侵犯者预后较差.