hOGG1: A novel mediator in nitrosamine-induced esophageal tumorigenesis.

BACKGROUND: The effect of human 8-Oxoguanine DNA Glycosylase (hOGG1) on exogenous chemicals in esophageal squamous cell carcinoma (ESCC) remain unclear. The study plans to determine hOGG1 expression levels in ESCC and possible interactions with known environmental risk factors in ESCC. MATERIAL AND METHODS: We analyzed levels of exposure to urinary nitrosamines in volunteers from high and low prevalence areas by GC-MS. And we performed the interaction between hOGG1 gene and nitrosamine disinfection by-products by analyzing hOGG1 gene expression in esophageal tissues. RESULTS: In ESCC, nitrosamine levels were significantly increased and hOGG1 mRNA expression levels were significantly decreased. There was a statistically significant interaction between reduced hOGG1 mRNA levels and non-tap drinking water sources in ESCC. The apparent indirect association between ESCC and NMEA indicated that 33.4% of the association between ESCC and NMEA was mediated by hOGG1. CONCLUSION: In populations which exposed to high levels of environmental pollutants NDMA, low expression of hOGG1 may promote the high incidence of esophageal cancer in Huai'an. hOGG1 may be a novel mediator in nitrosamine-induced esophageal tumorigenesis.

Comparation of the outcomes between ProGlide based post-closure technique and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation decannulation.

PURPOSE: To compare outcomes between post-closure technique based on ProGlide and arteriotomy repair for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation in this study. MATERIALS AND METHODS: Patients who received VA-ECMO treatment and successfully removed from its support in Changhai Hospital from January 2018 to December 2021 were included in this study. Patients was divided into post-closure group and surgical repair group according to the artery access closure method used. Clinical data of these patients were retrospectively collected and analyzed. RESULTS: A total of 58 patients were eventually enrolled in this study, including 26 (44.83%) patients in post-closure group and 32 (55.17%) patients in surgical repair group. Post-closure group had shorter procedure time, less minor bleeding events, estimated blood loss and packed cells transfused compared with the surgical repair group. The intensive care unit (ICU) length of stay after decannulation and the hospital length of stay after ICU in post-closure group were both shorter than surgical repair group. Nine patients (15.52%) died of multiple system organ failure after decannulation in this cohort and there were no significant differences between two groups. CONCLUSIONS: Our study showed the post-closure technique based on ProGlide for VA-ECMO decannulation is feasible, safe and effective.

Effect of preoperative pulmonary artery pressure on the prognosis of end-stage heart failure patients after heart transplantation.

OBJECTIVE: To evaluate the effect of preoperative pulmonary artery pressure on perioperative outcome of end-stage heart failure patients undergoing heart transplantation. METHODS: Retrospective analysis was undertaken on the clinical data of patients receiving heart transplantation in the Department of Cardiovascular Surgery of our hospital from March 2017 to March 2022. A ROC curve analysis was developed between mean pulmonary artery pressure (mPAP) and postoperative mortality using mPAP as diagnostic criteria. Patients were divided into groups based on this threshold to determine the best mPAP threshold value for predicting postoperative nosocomial mortality, and the differences in preoperative and intraoperative data, postoperative complications, and clinical prognosis of patients in the two groups were compared. Patients were followed up to draw the survival curve of patients in the two groups. RESULTS: The study enlisted the participation of 105 patients. ROC curve research revealed that preoperative pulmonary artery pressure was substantially linked with death following heart transplantation, with mPAP = 30.5mmHg being the best threshold. The group with mPAP ≥ 30.5mmHg had a greater incidence of postoperative ECMO support (28.2% vs. 10.6%, P = 0.021) and a higher incidence of in-hospital mortality (15.4% vs. 1.5%, P = 0.019) than the group with mPAP < 30.5mmHg. The postoperative survival rates of 105 patients were 91.3%, 88.7%, 81.6%, and 77.5% at 1, 2, 3, and 4 years, respectively, however, there was no significant difference between the two groups of patients in the postoperative intermediate-far survival rate (P = 0.431). CONCLUSIONS: Preoperative pulmonary artery pressure in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off mPAP value in predicting perioperative prognosis of heart transplant recipients is 30.5mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.

Transjugular Transcatheter Tricuspid Valve Implantation of LuX-Valve Bioprosthesis in a Preclinical Model.

The purpose of this preclinical study in a sheep model was to confirm the feasibility and safety of the LuX-Valve transjugular tricuspid valve (TV) replacement apparatus and to optimize the implantation procedure before beginning first-in-man study. The LuX-Valve was implanted in a sheep model (n = 8) via transjugular approach. Six of eight sheep underwent successful implantation procedure on beating heart. The first two sheep died during the prostheses deployment. In the remaining 6 sheep that survived, postoperative echocardiography results showed there was no paravalvular leakage (PVL) and central tricuspid regurgitation in 5 animals, whereas 1 animal had mild PVL. The mean transvalvular gradient was 1.1 ± 0.9 mm Hg at the 4-week follow-up. No right ventricular outflow tract (RVOT) obstruction, device malposition, pericardial effusion, coronary artery compression, or arrhythmias were observed. This technology may be a promising alternative for TR patients who are at high risk for open-heart surgery. Transjugular tricuspid valved-stent implantation. a Transjugular tricuspid valve replacement in a sheep model. b and c Valved stent. d, e, and f Schematic depiction of the implantation procedure.

The prognosis of preoperative preemptive intubation for acute type A aortic dissection patients: a retrospective propensity score matching study.

Background: Acute type A aortic dissection (AADA) is a life-threatening cardiovascular disease, and improving perioperative mortality remains a significant challenge. The purpose of this study is to investigate the impact of preemptive intubation under adequate sedation and analgesia on the prognosis of AADA patients under the high rupture risk. Methods: The medical records of patients diagnosed with AADA and admitted to Changhai Hospital from January 2019 to January 2020 were retrospectively reviewed. Patients were divided into two groups based on whether they received preoperative preemptive intubation in the cardiac intensive care unit (ICU) before surgery. We used propensity score matching (PSM) analysis to conduct statistical analyses on the preoperative, intraoperative, and postoperative clinical data of the two groups. Results: A total of 134 patients were eventually included in the study. One patient (3.8%) in the pre-intubation group and 15 (13.9%) in the control group died of dissection rupture before surgery. After excluding patients with dissection rupture, there were 25 patients in the pre-intubation group and 93 patients in the non-intubation group. After PSM, there were 17 patients in the pre-intubation group and 68 patients in the non-intubation group. Baseline data analysis showed that the pre-intubation group had a higher Sequential Organ Failure Assessment (SOFA) score (10.2±3.9 vs. 8.0±4.7, P=0.036) and a higher proportion of patients with coronary artery disease (16.0% vs. 1.1%, P=0.007). The rate of massive pericardial effusion was also higher in the intubation group (28.0% vs. 10.8%, P=0.049), and preoperative oxygenation index was lower (273.2±97.3 vs. 322.1±100.9, P=0.032) compared to the control group. The results showed no significant differences in intraoperative and postoperative data for the two groups. Kaplan-Meier survival curves indicated a trend towards a more favorable prognosis for patients in the preemptive intubation group, but this difference was not significant either before or after PSM. Conclusions: Preemptive pre-intubation may benefit high-risk patients with factors such as hypoxia, massive pericardial effusion, and agitation, improving the more critically AADA patients' perioperative outcomes.

Pulmonary and tricuspid regurgitation after Tetralogy of Fallot repair: A case report.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common congenital heart defects, and surgery is the primary treatment. There are no precise guidelines on the treatment protocol for tricuspid regurgitation (TR) as a common complication of TOF repair. The timing for treatment in patients presenting with valve regurgitation after TOF repair is often difficult to determine. Here, we report the first case of sequential treatment of pulmonary and TR using interventional therapy. CASE SUMMARY: We present the case of a 52-year-old female patient, who had a history of TOF repair at a young age. A few years later, the patient presented with pulmonary and tricuspid regurgitation. The symptoms persisted and TR worsened following percutaneous pulmonary valve implantation. Preoperative testing revealed that the patient's disease had advanced to an intermediate to advanced stage and that her general health was precarious. Because open-heart surgery was not an option for the patient, transcatheter tricuspid valve replacement was suggested. This procedure was successful, and the patient recovered fully without any adverse effects. This case report may serve as a useful resource for planning future treatments. CONCLUSION: Treatment of both valves should be considered in patients with tricuspid and pulmonary regurgitations following TOF repair. The interventional strategy could be an alternative for patients with poor general health.

Injectable conductive hydrogel can reduce pacing threshold and enhance efficacy of cardiac pacemaker.

Background: Pacemaker implantation is currently used in patients with symptomatic bradycardia. Since a pacemaker is a lifetime therapeutic device, its energy consumption contributes to battery exhaustion, along with its voltage stimulation resulting in local fibrosis and greater resistance, which are all detrimental to patients. The possible resolution for those clinical issues is an injection of a conductive hydrogel, poly-3-amino-4-methoxybenzoic acid-gelatin (PAMB-G), to reduce the myocardial threshold voltage for pacemaker stimulation. Methods: PAMB-G is synthesized by covalently linking PAMB to gelatin, and its conductivity is measured using two-point resistivity. Rat hearts are injected with gelatin or PAMB-G, and pacing threshold is evaluated using electrocardiogram and cardiac optical mapping. Results: PAMB-G conductivity is 13 times greater than in gelatin. The ex vivo model shows that PAMB-G significantly enhances cardiac tissue stimulation. Injection of PAMB-G into the stimulating electrode location at the myocardium has a 4 times greater reduction of pacing threshold voltage, compared with electrode-only or gelatin-injected tissues. Multi-electrode array mapping reveals that the cardiac conduction velocity of PAMB-G group is significantly faster than the non- or gelatin-injection groups. PAMB-G also reduces pacing threshold voltage in an adenosine-induced atrial-ventricular block rat model. Conclusion: PAMB-G hydrogel reduces cardiac pacing threshold voltage, which is able to enhance pacemaker efficacy.

Transcatheter tricuspid valve replacement in patients with severe tricuspid regurgitation.

OBJECTIVE: Tricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR. METHODS: This was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients' data at baseline, before discharge, 30 days and 6 months after the procedure were collected. RESULTS: All patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.0 (1.0, 4.0) days. 6-month mortality was 17.4%. Device migration occurred in one patient (2.4%) during follow-up. Transthoracic echocardiography at 6 months after operation showed TR was significantly reduced (none/trivial in 33, mild in 4 and moderate in 1) and the primary safety end point was achieved in 38 cases (82.6%). Patients suffered from peripheral oedema and ascites decreased from 100.0% and 47.8% at baseline to 2.6% and 0.0% at 6 months. CONCLUSIONS: The present study showed TTVR was feasible, safe and with low complication rates in patients with severe TR.

Impact of prosthesis-patient mismatch on early and late outcomes after mitral valve replacement: a meta-analysis.

BACKGROUND: Prognostic significance of prosthesis-patient mismatch (PPM) after mitral valve replacement (MVR) remains uncertain because of the limited studies reporting inconsistent or even contrary results. This meta-analysis pooled results of all available studies comparing early and late prognoses between patients with significant mitral PPM and those without. METHODS: Studies were identified by searching Pubmed, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Impact of PPM on postoperative hemodynamic results, thirty-day mortality, overall mortality, mortality of thirty-day survivors, and primary morbidity after MVR was evaluated via meta-analysis. Robustness of pooled estimates, source of heterogeneity, and publication bias were assessed via sensitivity analyses, meta-regression as well as subgroup analysis stratified according to methodological or clinical heterogeneity, or sequential omission method, and funnel plot or Begg's and Egger's tests, respectively. RESULTS: Nineteen cohort studies involving 9302 individuals (PPM group: n = 5109, Control group: n = 4193) were included for meta-analysis. Total PPM and severe PPM prevalence were 3.8%-85.9% and 1%-27%, with a mean value of 54.9% and 14.1%, respectively. As compared with control group, mitral PPM group demonstrated a poorer postoperative hemodynamic status of higher mean and peak residual transprosthetic pressure gradients (TPG), higher postoperative systolic pulmonary artery pressure (SPAP) and less reduction, higher postoperative pulmonary hypertension (PH) prevalence and less PH regression, smaller net atrioventricular compliance, less NYHA class decrease, higher postoperative functional tricuspid regurgitation prevalence and less regression. The PPM group also revealed a higher thirty-day mortality, long-term overall mortality, mortality of thirty-day survivors, and postoperative congestive heart failure prevalence, which were positively correlated with the severity of PPM if it was classified into tri-level subgroups. Left ventricular end-diastolic diameter, postoperative atrial fibrillation (AF) prevalence, and the AF regression were analogous between groups. Most pooled estimates were robust according to sensitivity analyses. Male patients and bioprosthesis implantation proportion were prominent source of between-study heterogeneity on thirty-day mortality. Publication bias was not significant in tests for all the outcomes, except for SPAP and TPG. CONCLUSIONS: Mitral PPM would result in poorer postoperative hemodynamics and worse early and late prognosis. Severe PPM must be avoided since deleterious impact of mitral PPM was severity dependent.

Surgical Outcomes of Stent-Related Type A Dissection Compared with Spontaneous Type A Dissection.

OBJECTIVE: Aortic endovascular stent implantation includes thoracic endovascular aortic repair (TEVAR), hybrid aortic repair (HAR), and ascending aorta stent implantation (AASI). In this study, we compared the surgical outcomes of stent-related type A dissection (SRTAD) compared with spontaneous type A dissection (STAD). METHODS: From July 2011 to July 2014, we identified 17 SRTAD patients received surgical repair in our institution. Propensity score-matching was used to identify 34 STAD patients as controls. RESULTS: Preoperative data of SRTAD group and STAD group had no statistical difference. Selective cerebral perfusion (SCP) time was longer in SRTAD group than in STAD group (P <0.05). SRTAD group had a longer cross-clamp time compared with STAD group (P <0.05). No intraoperative deaths in two groups. No differences in CPB time and concomitant procedures between two groups. In-hospital mortality was 11.76% (2 of 17) in SRTAD group and 2.9% (1 of 34) in STAD group (P <0.05). No differences were found in intensive care unit (ICU) time, ventilation, paraparesis, and other postoperative complications between SRTAD and STAD groups. No difference was found in survival rate between SRTAD and STAD groups in the postoperative 1-year follow-up. CONCLUSIONS: SRTAD patients received surgical repair had a higher in-hospital mortality compared with STAD, but no differences were found in postoperative complications and mid-term outcomes.

[Expression patterns of ectodysplasin and ectodysplasin receptor during early dental development in zebrafish].

OBJECTIVE: This study aims to study the expression patterns of ectodysplasin (EDA) and ectodysplasin receptor (EDAR) during the early development of zebrafish and provide a foundation for further research of the Eda signaling pathway in tooth development. METHODS: Total RNA was extracted from zebrafish embryos at 48 hours postfertilization (hpf) and then reverse transcribed for cDNA library generation. The corresponding RNA polymerase was selected for the synthesis of the digoxin-labeled antisense mRNA probe of zebrafish pharyngeal tooth specific marker dlx2b and Eda signaling-associated genes eda and edar in vitro. The three sequences were ligated into a pGEMT vector with a TA cloning kit, and polymerase chain reaction (PCR) was applied to linearize the plasmid. The resultant PCR sequences were used as templates for synthesizing Dig-labeled mRNA probe dlx2b, eda, and edar. Zebrafish embryos were collected at 36, 48, 56, 60, 72, and 84 hpf, then whole mount in situ hybridization was performed for the detection of eda and edar expression patterns. Then, their expression patterns at 72 hpf were compared with the expression pattern of dlx2b. RESULTS: The mRNA antisense probes of dlx2b, eda, and edar were successfully obtained. The positive signals of eda and edar were observed in zebrafish pharyngeal tooth region at 48-72 hpf and thus conform to the signals of dlx2b in the positive regions. CONCLUSIONS: The ligand eda and edar, which are associated with the Eda signaling pathway, are strongly expressed only at the pharyngeal tooth region in zebrafish from tooth initiation to the morphogenesis stage. Thus, the Eda signaling pathway may be involved in the regulation of the early development of zebrafish pharyngeal teeth.

Retrograde Type A Dissection after Ascending Aorta Involved Endovascular Repair and Its Surgical Repair with Stented Elephant Trunk.

BACKGROUND: Retrograde type A dissection (RTAD) is a serious complication after ascending aorta involved endovascular repair (AAIER). We here report our surgical approach to this serious complication. METHODS: From July 2011 to July 2014, 8 RTADs after AAIER patients received surgical repair in our institution. Data of these RTAD patients were retrospectively collected for further analysis. All patients received urgent surgical repair based on the stented elephant trunk technique. We took 2 different ways to handle the previous stent during operation. In patients who had a prior hybrid aortic repair, we removed the proximal part of the stent while the distal part was left in place. In patients who had prior ascending aorta stent implantation (AASI), the stent was totally removed. RESULTS: The mean age of the patients was 57.6 ± 11.9 years. Regarding the index intervention, 2 patients received hybrid aortic repair and 6 patients received AASI. In patients who received AASI, 1 patient underwent simultaneous thoracic endovascular aortic repair (TEVAR) and another patient received simultaneous chimney technique in innominate artery and left common carotid artery combined with bypass from left subclavian artery to left common carotid artery to cure the type I endoleak induced by the previous implanted TEVAR stent. All patients received a new elephant trunk implantation during surgical repair. The mean cardiopulmonary bypass, selective cerebral perfusion, and aortic cross-clamp time were 172.1 ± 13.3, 40.8 ± 4.2, and 121.8 ± 11.4 min, respectively. The mean intensive care unit time was 7.8 ± 3.4 days. Two patients (25.0%) experienced transient neurologic dysfunction and recovered completely before discharge. In-hospital death rate was 12.5% (1 of 8). The mean follow-up time was 17.1 ± 9.5 months. No late deaths or complications occurred during follow-up. CONCLUSIONS: AAIER especially AASI used in aortic dissection treatment should be seriously considered since RTAD might occur. Our study indicated that surgical repair with stented elephant trunk was feasible and according to the cause of RTAD, different surgical strategies should be taken to manage the stent.

Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection.

BACKGROUND: Preoperative hypoxemia is a frequent complication of acute Stanford type A aortic dissection (ATAAD). The aim of the present study was to determine which factors were associated with hypoxemia. METHODS: A series of data were collected in a statistical analysis to evaluate preoperative hypoxemia in patients with ATAAD. After retrospectively analyzing data for 172 patients, we identified the risk factors for preoperative hypoxemia. Hypoxemia was defined by an arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio of 200 or lower. Subsequent to identifying the patient population, a prospective study was conducted using ulinastatin as a preoperative intervention. The ulinastatin group received ulinastatin at a total dose of 300,000 units prior to surgery. All the pertinent factors were investigated through univariate and multiple logistic regression analysis. RESULTS: The factors associated with preoperative hypoxemia in ATAAD comprised the following: body mass index (BMI) ≥25; white blood cell count (WBC) and neutrophil counts; levels of C-reactive protein (CRP), D-dimer, and interleukin-6 (IL-6); ATAAD involving the celiac trunk, renal artery, or mesenteric artery. Logistic regression analysis showed that CRP and IL-6 levels were independent predictive factors. We found that ulinastatin effectively could improve oxygenation, since compared to the control group the oxygenation in the ulinastatin group was significantly improved. CONCLUSIONS: Systemic inflammatory reactions played a vital role in preoperative hypoxemia after the onset of ATAAD. The oxygenation of the patient could be improved significantly by inhibiting the inflammatory response prior to surgery.

Mechanisms of aortic dissection smooth muscle cell phenotype switch.

OBJECTIVE: To investigate the expression of Nanog homeobox (NANOG) in thoracic aortic dissection (TAD) and the role of NANOG in regulating human aortic vascular smooth muscle cells (VSMCs) phenotype switch. METHODS: Aortic specimens were collected from 20 patients undergoing TAD and 10 controls. VSMCs were isolated by adherent cultivation approach. The expression of NANOG, osteopontin (OPN), and VSMCs phenotype markers were determined by quantitative real-time polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence. Cell counting, scratch wound-healing assay, Transwell migration, and apoptosis assays were used for cell function assessment. Deoxyribonucleic acid-protein binding detection was performed by chromatin immunoprecipitation. RESULTS: Our experiment results showed that NANOG and OPN were highly expressed in TAD aortic wall and VSMCs, both accompanying VSMCs phenotype switch. Overexpression of NANOG induced the up-regulation of VSMCs synthetic marker matrix metalloproteinase 2 and the down-regulation of VSMCs contractile markers α-smooth muscle actin and smooth muscle 22α. Overexpression of NANOG also enhanced the proliferation, migration, and antiapoptosis capabilities of VSMCs. The results also showed that these functions of NANOG was via OPN and NANOG directly up-regulated OPN by binding to its promoter region. CONCLUSIONS: Our study suggests that NANOG is highly expressed in TAD aortic wall and VSMCs. Increased NANOG promotes VSMCs phenotype switch by directly up-regulating OPN through binding to its promoter region.

Risk factors of pre-operational aortic rupture in acute and subacute Stanford type A aortic dissection patients.

BACKGROUND: Aortic rupture is one of the main causes of early death in acute and subacute Stanford type A aortic dissection (ATAAD) patients. This study aimed to analyze potential risk factors for pre-operational aortic rupture in ATAAD patients. METHODS: We retrospectively reviewed aortic dissection cases treated between May 2013 and May 2016 in Changhai Hospital, Shanghai. A total of 329 patients with ATAAD were included in the final analysis, and 31 patients died of aortic rupture before surgery. Clinical data on basic characteristics, clinical presentation, and biochemical measurements for all 329 patients were analyzed. RESULTS: The in-hospital aortic rupture rate was 9.4% (31/329), and the rupture accounted for 47% (31/66) of all in-hospital deaths of ATAAD patients. Patients who experienced rupture were significantly older (P<0.001), had lower systolic blood pressure (P=0.040), had more painful manifestation (P<0.001), had more systematic complications [shock (P=0.001), coma (P<0.001), hypoxemia (P=0.006), kidney and liver dysfunctions, and myocardial injury (higher troponin, P=0.009)], and had worse blood coagulability [lower platelet count (P=0.012), longer prothrombin time (P<0.001), and higher D-dimer (P=0.003)]. Multivariable analysis identified the following independent risk factors: shock [odds ratio (OR): 8.12; 95% confidence interval (CI), 1.10-59.85, P=0.040], pain requiring medication (OR: 12.67; 95% CI, 2.43-66.09; P=0.003), troponin level >0.7 ng/mL (OR: 9.28; 95% CI, 1.72-50.06; P=0.010), and D-dimer level ≥10 µg/mL (OR: 13.37; 95% CI, 2.18-81.97; P=0.005). CONCLUSIONS: Aortic rupture accounted for 47% of all in-hospital deaths among patient with ATAAD. Shock, pain requiring medication, a troponin level >0.7 ng/mL and a D-dimer level ≥10 µg/mL are independent risk factors for aortic rupture in these patients.

Angiogenin elevates the invasive potential of squamous cell lung carcinoma cells through epithelial­mesenchymal transition.

Squamous cell carcinoma of the lung is one of the most aggressive cancers, and its aggressiveness is in part due to its intrinsic high rate of metastasis. Moreover, the process of epithelial-mesenchymal transition (EMT) appears to be involved in these neoplastic processes. Furthermore, EMT-type cells share many biological characteristics with the function of angiogenin (ANG) in squamous cell lung carcinoma. We conducted immunohistochemical analysis to detect the expression of ANG, E-cadherin, vimentin, N-cadherin, ß-catenin and TGF-ß1 in 60 cases of squamous cell lung carcinoma tissues. Western blot analysis was adopted to detect the protein expression levels of ANG and EMT markers. The effects of ANG on proliferation, migration and invasion of squamous cell lung carcinoma cells was analyzed by Cell Counting Kit-8, scratch assay and Transwell invasion chamber in order to reveal the role of ANG in the process of EMT in squamous cell lung carcinoma. The results revealed that ANG was aberrantly expressed in the squamous cell lung carcinoma specimens and was closely correlated with the differentiation of the cell lines. The expression of ANG was also significantly associated with metastasis and the stage of the squamous cell lung carcinoma cases. In addition, we validated that ANG influenced the expression of vimentin, E-cadherin, N-cadherin, ß-catenin and TGF-ß1 in SK-MES-1 cells. Most importantly, overexpression of ANG enhanced the migration and invasion of SK-MES-1 cells, while knockdown resulted in opposite effects. In the present study, we found that ANG plays an important role in EMT in squamous cell lung carcinoma and may be a valuable therapeutic target for squamous cell lung carcinoma.

Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells.

The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next, autophagic activity was examined in AD mice model established by ß-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD.