Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). MiR-142-3p overexpression increased DOX sensitivity and enhanced DOX-induced apoptosis in breast cancer cells. High-mobility group box 1 (HMGB1) is a direct functional target of miR-142-3p in breast cancer cells and miR-142-3p negatively regulated HMGB1 expression. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by miR-142-3p up-regulation. In conclusion, miR-142-3p overexpression may inhibit autophagy and promote the drug sensitivity of breast cancer cells to DOX by targeting HMGB1. The miR-142-3p/HMGB1 axis might be a novel target to regulate the drug resistance of breast cancer patients.

Objective: To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) . Methods: From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively. Results: Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) . Conclusion Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

Perioperative fluid therapy is an important part of anesthesia management.Its main purpose is to maintain the perfusion of organs and tissues,ensure the balance of oxygen supply and demand,protect the function of organs and promote the rapid recovery of patients.Underload or overload of perioperative fluid infusion can affect the prognosis of patients during thoracic surgery.It is the basis of fluid management to using appropriate methods to accurately monitor of hemodynamic parameters.Goal-directed fluid therapy (GDFT),with hemodynamic parameters as targets,maximizes perioperative stroke volume through fluid loading.It plays an important role in accelerating patient recovery and reducing hospital stay and has been widely used in clinical.This article will review the progress of perioperative fluid management characteristics and circulatory function monitoring methods in thoracic surgery in order to provide guidance for clinical work.

Objective: To evaluate the results of catheter ablation of ventricular tachycardia (VT) via direct ventricle puncture access in patients without traditional approach. Methods: Two idiopathic left fasicular VT patients with mechanical aortic and mitrial valve repalcement and 1 patient with right ventricular originated VT post mechanical tricuspid valve repalcement from March 2010 to July 2012 in Fuwai hospital were enrolled in this study. For left fasicular VT patients, catheter ablation was performed using transapical left ventricular access via minithoracotomy. For the patient with right ventricular originated VT, catheter ablation was performed via percutaneous right ventricle puncture at xiphoid. Abaltion was guided under EnSite NavX mapping system. The feasibility of VT ablation via direct ventricle puncture access and long-term VT recurrence were investigated. Results: Catheter ablation was successful in all patients, and all clinical VTs were eliminated. The procedure time was 53, 62 and 74 minutes respectively with radiation time 11, 16 and 20 minutes. The ablation time was 130, 170 and 240 seconds individually. No procedure related complication occurred. After a follow-up time of 76, 55 and 82 months respectively, no VT recurrence was found in patients with left fasicular VT. New-onset VT with different morphology with previous VT was recorded in the patient with right ventricular originated VT, subcutaneous implantable defibrillator was implanted finally in this patient. Conclusions For patients with endocardial origined ventricular arrhythmias which could not be ablated via traditional approaches, direct ventricle puncture access with hybrid techniques provides a new approach foreliminating VTs in these patients.

Objective: To evaluate the safety and feasibility of hybrid thoracoscopic surgery and catheter ablation in treating the patients of long-standing persistent atrial fibrillation (AF) with preliminary experience. Methods: A total of 15 consecutive relevant patients treated in our hospital by hybrid thoracoscopic surgery and catheter ablation from 2014-04 to 2016-03 were studied. The average AF time was (4.0±3.9) years including 13 male. All patients received thoracoscopic surgical ablation including pulmonary vein isolation, left atrial (LA) posterior wall isolation, Waterston's groove Ganglionated plexi ablation by bipolar radiofrequency ablation clamp and LA appendage removal, Marshall ligament dividing. Then establishing LA 3D-modeling, based on LA 3D voltage mapping, catheter ablation was conducted to reinforce surgical ablation or modification in order to confirm bidirectional blocking. Meanwhile, LA ridge and mitral isthmus ablation was performed, some patients received LA anterior wall and tricuspid isthmus ablation. The patients were followed-up at 3, 6 and 12 months after the procedure. Results: 13 patients were restored to sinus rhythm after the procedure and no operative complications occurred. The average follow-up time was (12.1±11.5) months. 2 patients with recovered sinus rhythm had re-catheter ablation since atrial flutter at 3 months post-procedure and sinus rhythm was restored. The overall success rate was 86.7% (13/15), no patient had anti-arrhgthmia medication. Conclusion: Hybrid thoracoscopic ablation and catheter ablation have been a minimally invasive, safe and effective method in treating the patients of long-standing persistent AF.

Objective: To study the safety and efifcacy of hematoma aspiration with manual compression for treating the patients of femoral pseudoaneurysm after cardiac catheterization under ultrasound guidance. Methods: A total of 27 patients suffering from post-catheterization iatrogenic femoral pseudoaneurysm were analyzed including 14 male and 13 female at the mean age of (53.5±11.4) years. The body, neck and blood supply area of pseudoaneurysm were located by ultrasonography; 18 gauge needle was punctured into the center of pseudoaneurysm to aspirate blood, meanwhile the neck and body of pseudoaneurysm were manually compressed to block blood supply for relevant artery under ultrasound guidance. Manual compression was conducted for 15 min followed by bandage compression; the patients were lie on the back and kept lower extremity straight for 12 hours. Ultrasonography was performed at 24 hours and 1 month after the operation in all patients respectively. Results: There were 24/27 (88.9%) patients having successful aspiration with manual compression at ifrst time; 2 (7.4%) having incomplete occlusion at ifrst time and the success was obtained by second time; 1 having incomplete occlusion due to coexisted femoral arteriovenous ifstula, while the body of pseudoaneurysm was obviously decreased. The overall success rate was 96.3% (26/27), no procedural complication occurred. Conclusion Ultrasonography guided hematoma aspiration with manual compression has been safe and effective for treating the patients of iatrogenic femoral pseudoaneurysm.

To explore the safety and efficacy of left atrial appendage (LAA) occlusion under the guidance of local anesthesia and modified transseptal puncture technology by coronary sinus assisted positioning in patients with nonvavular atrial fibrillation (NVAF). Methods: A total of 16 NVAF patients received local anesthesia and percutaneous LAmbre or Amplatzer cardiac plug occluder implantation. There were 12 males and the patients mean age was at (71.0±6.0) years with CHA2DS2-VASc score at (4.1±1.5); all patients had walfarin contradiction or with walfarin related side effect. Transseptal puncture was conducted by coronary sinus catheter as the anatomic location marker. Results: All 16 patients finished transseptal puncture and no relevant complication occurred. 15/16 (93.8%) patients had successful LAA occlusion, 1 patient was abandoned because of LAA anatomic structure variation. The mean operative time was (65.0±23.0) min and the mean X-ray exposure time was (12.0±3.0) min. The mean diameter of occluder was (32.5±6.0)mm. Conclusion: LAA occlusion was safe and effective with local anesthesia and modified transseptal puncture technology by coronary sinus assisted positioning in relevant patients.

OBJECTIVE:To explore the effects of early treatment with mouse nerve growth factor on the wound healing in aged patients with electric burn. METHODS:78 elderly patients with electric burn were divided into control group and observation group by random number table method,with 39 cases in each group. Control group was given routine method for electric burn, and observation group was additionally given Mouse nerve growth factor for injection 30 μg dissolved in 2 ml 0.9% Sodium chlo-ride injection within 24 h,im,qd,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Clinical effica-cies of 2 groups were compared as well as VAS score before treatment,3,5,7 days after treatment. The survival rate of skin flaps and the rate of wound healing 3,5,7 days after treatment,the recovery of wound scar,the value of wound blood perfusion,the time of complete wound healing and the occurrence of ADR were also compared. RESULTS:The total effective rate of observation group(94.9%)was significantly higher than that of control group(66.7%),with statistical significance(P<0.05). 3,5,7 days after treatment,VAS score of observation group was significantly lower than that of control group,and the survival rate of skin flaps and the rate of wound healing were significantly higher than those of control group,with statistical significance(P<0.05). Af-ter treatment,VSS score of observation group was significantly lower than that of control group,while the value of wound blood perfusion was significantly higher than that of control group;the time of complete wound healing was significantly lower than that of control group,with statistical significance (P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Early treat-ment with mouse nerve growth factor for elderly patients with electric burns can effectively lower the VAS and VSS score,improve the survival rate of skin flaps and the rate of wound healing,increase the value of wound blood perfusion and shorten the time of complete wound healing with good clinical efficacy and safety.

Background One of the major challenges in arrhythmogenic right ventricular cardiomyopathy (ARVC) ablation is ventricular tachy-cardia (VT) non-inducibility. The study aimed to assess whether fast rate (≥ 250 beats/min) right ventricular burst stimulation was useful for VT induction in patients with ARVC.Methods Ninety-one consecutive ARVC patients with clinical sustained VT that underwent electro-physiological study were enrolled. The stimulation protocol was implemented at both right ventricular apex and outflow tract as follows: Step A, up to double extra-stimuli; Step B, incremental stimulation with low rate (< 250 beats/min); Step C, burst stimulation with fast rate (≥ 250 beats/min); Step D, repeated all steps above with intravenous infusion of isoproterenol.Results A total of 76 patients had inducible VT (83.5%), among which 49 were induced by Step C, 15 were induced by Step B, 8 and 4 by Step A and D, respectively. Clinical VTs were induced in 60 patients (65.9%). Only two spontaneously ceased ventricular fibrillations were induced by Step C. Multivariate analysis showed that a narrower baseline QRS duration under sinus rhythm was independently associated with VT non-inducibility (OR: 1.1; 95% CI: 1.0–1.1;P = 0.019).ConclusionFast rate (≥ 250 beats/min) right ventricular burst stimulation provides a useful supplemental method for VT induction in ARVC patients.