Recombinant Human Hepatocyte Growth Factor Plasmids for Treating Patients with Chronic Limb Threatening Ischaemia: A Systematic Review and Meta-analysis.

OBJECTIVE: Recombinant human hepatocyte growth factor (HGF) plasmids are novel alternatives to salvage limbs in patients with chronic limb threatening ischaemia (CLTI). A systematic review and meta-analysis of data were conducted to assess the therapeutic efficacy of HGF plasmids in patients with CLTI. DATA SOURCES: Randomised controlled studies evaluating HGF plasmid efficacy in patients with CLTI were identified using Medline, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases. REVIEW METHODS: Meta-analyses of the reported relative risks (RR) or mean differences (MD) were conducted. Subgroup analyses determined the efficacy of HGF plasmids in cohorts excluding Buerger's disease. Certainty of evidence for each outcome was assessed. RESULTS: Seven studies (n = 655) were included. Based on low certainty evidence, patients treated with HGF had a significantly higher complete ulcer healing rate (RR 1.99, 95% CI 1.30 - 3.04; p = .015) than patients treated with placebo. The HGF treatment was associated with reduced visual analogue scale (VAS) scores of pain severity (MD -1.56, 95% CI -2.12 - -1.00; p < .001) vs. placebo in patients with CLTI assessed at the 3 month follow up (low certainty evidence); no significant differences were observed in major amputation (RR 0.91, 95% CI 0.48 - 1.73; p = .77) (low certainty evidence), or all-cause mortality (RR 0.93, 95% CI 0.38 - 2.27; p = .87) (low certainty evidence) between patients treated with HGF and placebo. Low certainty evidence suggested no significant differences in change in ankle-brachial index at 6 months (MD 0.00, 95% CI -0.09 - 0.09; p = 1.0) between patients treated with HGF and placebo. The complete ulcer healing rate and improved 3 month VAS scores of pain severity benefits persisted in subgroup analyses (low certainty evidence). CONCLUSION: Hepatocyte growth factor treatment is associated with an increased complete ulcer healing rate and reduced ischaemic pain in patients with CLTI.

Deubiquitylase USP9X maintains centriolar satellite integrity by stabilizing pericentriolar material 1 protein.

Centriolar satellites are small cytoplasmic granules that play important roles in regulating the formation of centrosomes and primary cilia. Ubiquitylation of satellite proteins, including the core satellite scaffold protein pericentriolar material 1 (PCM1), regulates centriolar satellite integrity. Currently, deubiquitylases that control centriolar satellite integrity have not been identified. In this study, we find that the deubiquitylase USP9X binds PCM1, and antagonizes PCM1 ubiquitylation to protect it from proteasomal degradation. Knockdown of USP9X in human cell lines reduces PCM1 protein levels, disrupts centriolar satellite particles and causes localization of satellite proteins, such as CEP290, to centrosomes. Interestingly, knockdown of mindbomb 1 (MIB1), a ubiquitin ligase that promotes PCM1 ubiquitylation and degradation, in USP9X-depleted cells largely restores PCM1 protein levels and corrects defects caused by the loss of USP9X. Overall, our study reveals that USP9X is a constituent of centriolar satellites and functions to maintain centriolar satellite integrity by stabilizing PCM1.

A systematic review and meta-analysis on the association between C-reactive protein levels and adverse limb events after revascularization in patients with peripheral arterial disease.

OBJECTIVE: Patients with peripheral arterial disease (PAD) are predisposed to postprocedure adverse limb events (ALE). Previous single-center studies investigating the relationship between baseline C-reactive protein (CRP) levels and postprocedure ALE have reported inconsistent results. Therefore, we performed a systematic review and meta-analysis of reported data to determine the association between CRP levels and the occurrence of postprocedure ALE in patients with PAD. METHODS: Studies investigating the association between the CRP levels and postprocedure ALE (ie, target vessel revascularization, amputation, restenosis, disease progression, composite endpoint of any of these ALE) were identified in the Medline, EMBASE, and Cochrane databases. Meta-analyses of the reported hazard ratios (HRs) were conducted using an inverse variance-weighted random effects model. Subgroup analyses were performed to determine the differences in outcomes between open surgery and endovascular treatment. Pooled estimates are reported as HRs to compare higher and lower CRP levels and odds ratio or relative risk per unit increase in logeCRP (natural logarithm C-reactive protein). RESULTS: A total of eight studies involving 1460 participants were included in our meta-analysis. Patients with higher baseline CRP levels had a greater risk of ALE (HR, 1.09; 95% confidence interval, 1.00-1.18; P = .04) compared with those with lower baseline CRP levels. The pooled estimate of odds ratio and relative risk for ALE was 2.25 (95% confidence interval, 1.49-3.41; P < .01) per unit increase in logeCRP. Subgroup analyses found no significant differences in the pooled estimates in studies of open surgery vs endovascular treatment. CONCLUSIONS: Our results have demonstrated that high baseline CRP levels are predictive of ALE in patients with PAD after lower limb revascularization.

[Treatment of Concomitant Intra-abdominal Malignancy and Abdominal Aortic Aneurysm].

Objective To explore the outcomes in patients who receive the endovascular abdominal aortic aneurysm repair(EVAR)and have concomitant intra-abdominal malignancy.Methods Between January 2014 and December 2019,all the patients who underwent surgery for malignancy and/or EVAR were retrospectively reviewed.Results Twenty-eight abdominal aortic aneurysm(AAA)patients with concomitant intra-abdominal malignancy were included.The patients were treated by two-stage operation and the priority was given for EVAR in 21 patients.There was no perioperative death or major complications.In the follow-up,one patient developed graft thrombosis and one had type Ⅱ endoleak.There was no AAA-associated death.Conclusions It is preferred that EVAR should come first followed by operation for malignancy.Details of treatment strategy still need further investigation.

Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation.

APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer genomes, including those of cervical and head and neck cancers caused by human papillomavirus (HPV) infection. However, the driving forces that promote off-target A3 activity remain mostly unclear. Here, we report a mechanism for the dramatic increase of A3A protein levels in HPV-positive keratinocytes. We show that expression of the viral protein E7 from high-risk HPVs, but not E7 from low-risk HPVs, significantly prolongs the cellular half-life of A3A protein in human keratinocytes and HPV-positive cancer cell lines. We have mapped several residues within the cullin 2 (CUL2) binding motif of HPV16 E7 as being important for mediating A3A protein stabilization. Furthermore, we provide direct evidence that both A3A and HPV16 E7 interact with CUL2, suggesting that the E7-CUL2 complex formed during HPV infection may regulate A3A protein levels in the cell. Using an in vitro cytidine deaminase assay, we show that E7-stabilized A3A remains catalytically active. Taken together, our findings suggest that the HPV oncoprotein E7 dysregulates endogenous A3A protein levels and thus provides novel mechanistic insight into cellular triggers of A3 mutations in HPV-positive cancers.IMPORTANCE Human papillomavirus (HPV) is causally associated with over 5% of all human malignancies. Several recent studies have shown that a subset of cancers, including HPV-positive head and neck and cervical cancers, have distinct mutational signatures potentially caused by members of the APOBEC3 cytidine deaminase family. However, the mechanism that induces APOBEC3 activity in cancer cells is poorly understood. Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner. Interestingly, the HPV E7-stabilized A3A protein maintains its deaminase activity. These findings provide a new insight into cancer mutagenesis enhanced by virus-induced A3A protein stabilization.

The Efficacy and Safety of AngioJet Rheolytic Thrombectomy in the Treatment of Subacute Deep Venous Thrombosis in Lower Extremity.

BACKGROUND: The aim of this study is to examine the efficacy and safety of AngioJet rheolytic thrombectomy for the treatment of subacute deep venous thrombosis (DVT) in lower limbs. METHODS: A retrospective study was performed on 90 patients with subacute DVT (15-90 days) in lower limbs in our center from November 2015 to December 2016. In total, 27 patients with subacute DVT in lower limbs treated with AngioJet rheolytic thrombectomy were included in the study, including 17 men and 10 women. The onset time of thrombosis was between 15 and 75 days. Five patients were diagnosed bilaterally; 5 patients were diagnosed in the right lower limb; and 17 patients were affected by thrombosis in left lower limb. All the 27 cases received AngioJet rheolytic thrombectomy. RESULTS: After AngioJet thrombectomy, 17 cases were improved to grade II (50-99%), and 10 cases were grade I (<50%). Nineteen cases were treated with subsequent catheter-directed thrombolysis (CDT), and the average time of thrombolysis was 3.2 days, with an average urokinase administration dose of 7.32 million units. Among the 27 cases, 21 of them received iliac venous balloon dilation, with 10 of them being implanted with the iliac vein stent; 12 stents were implanted in total. Finally, the angiography suggested that 25 cases (92.6%) obtained a recanalization rate higher than grade II, and no serious complications occurred during the perioperative period. All patients were followed up regularly for 3 to 15 months, and 2 patients died from malignant tumor during the follow-up period. Twenty-three cases were followed up for more than 6 months; 17 cases finished 12-month follow-up. The primary patency rate at 6 and 12 months was 96.3% and 88.9%, respectively. The Villalta score of postoperative postthrombosis syndrome symptom at 6 and 12 months was 3.3 ± 2.8 and 3.5 ± 2.8, respectively. CONCLUSIONS: It is safe and feasible to use the AngioJet rheolytic thrombectomy in the treatment of subacute DVT in lower limbs. In patients without high risk of bleeding, combination of AngioJet thrombectomy and CDT is an effective treatment to reduce the thrombus volume.

Endovascular Repair of Complex Aortoiliac Aneurysm with the Sandwich Technique in Sixteen Patients.

BACKGROUND: This study aimed to evaluate the safety and efficiency of the sandwich technique in endovascular repair of complex aortoiliac aneurysm. METHODS: Sixteen patients (mean age 69.6 years, ranging from 58 to 78 years) with complex aortoiliac aneurysm were studied retrospectively from October 2013 to September 2017 in two vascular centers of teaching hospitals. Computed tomography angiography (CTA) was performed to make individual therapy. They were all performed endovascular repair with sandwich technique, including one with the sandwich, chimney, and fenestrated techniques during the same procedure. All patients were followed up at 1 month, 3 months, 6 months, 12 months, and yearly thereafter with X-ray, ultrasound, and/or CTA. RESULTS: The initial technical success was 81.25%, and the assisted technical success was 100%. At final angiography, little flow of a type I and a type III endoleak was found in two patients with observation. Two type II endoleaks were also detected. During the perioperative period, two patients suffered myocardial infarction. One pulmonary infection and one urinary infection happened. No death or cerebrovascular events occurred. During the follow-up (mean 18 months, ranging from 2 to 45 months), three stent occlusions were detected. One case got reintervened for his external iliac artery stent thrombosis in the first month postoperatively. The other two were under observation. A readmission happened to one man for his right brachial artery pseudoaneurysm in the third month postoperatively. One patient died of nonaneurysmal related reason in the eighth month. No aneurysmal related death, rupture, or new endoleak was found. No paralysis, claudication, or bowel ischemia was complained of. The primary patency of the preserved branches were 94.7%, 92.0%, 92.0%, 92.0%, 92.0% separately in first, sixth, 12th, 24th, and 36th month. CONCLUSIONS: For patients who are not candidates for open surgery or conventional endovascular repair with complex aortoiliac aneurysm, the sandwich technique is a feasible alternative to management.

[Femoral-popliteal Arteriosclerosis Obliterans:Review of Evidence-based Studies on Drug-eluting Endovascular Treatment].

Atherosclerosis-related diseases have increasingly become health concerns with the increased living conditions and aging.Globally,about 200 million people have suffered from arteriosclerosis obliterans(ASO),which can even be life-threatening in some cases.The past seven decades have witnessed the rapid advances in the treatment of ASO,which has developed from surgery to endovascular interventions including plain balloon angioplasty,bare metal stent placement,drug-coated balloon,and drug-eluting stent.However,the roles of these new techniques for femoral-popliteal lesions,especially their real-world clinical outcomes and indications,remain unclear.This article reviews the latest evidences on the use of drug-eluting devices in treating femoral-popliteal arteriosclerosis obliterans.

Monoubiquitination of survival motor neuron regulates its cellular localization and Cajal body integrity.

Low levels of the survival motor neuron (SMN) protein cause spinal muscular atrophy, the leading genetic disorder for infant mortality. SMN is ubiquitously expressed in various cell types and localizes in both the cytoplasm and the nucleus, where it concentrates in two subnuclear structures termed Cajal body (CB) and gems. In addition, SMN can also be detected in the nucleolus of neurons. Mechanisms that control SMN sorting in the cell remain largely unknown. Here, we report that the ubiquitin (Ub) ligase Itch directly interacts with and monoubiquitinates SMN. Monoubiquitination of SMN has a mild effect on promoting proteasomal degradation of SMN. We generated two SMN mutants, SMN(K0), in which all lysines are mutated to arginines and thereby abolishing SMN ubiquitination, and Ub-SMN(K0), in which a single Ub moiety is fused at the N-terminus of SMN(K0) and thereby mimicking SMN monoubiquitination. Immunostaining assays showed that SMN(K0) mainly localizes in the nucleus, whereas Ub-SMN(K0) localizes in both the cytoplasm and the nucleolus in neuronal SH-SY5Y cells. Interestingly, canonical CB foci and coilin/small nuclear ribonucleoprotein (snRNP) co-localization are significantly impaired in SH-SY5Y cells stably expressing SMN(K0) or Ub-SMN(K0). Thus, our studies discover that Itch monoubiquitinates SMN and monoubiquitination of SMN plays an important role in regulating its cellular localization. Moreover, mislocalization of SMN disrupts CB integrity and likely impairs snRNP maturation.

Renal Function Preservation in Surgical Resection of Primary Inferior Vena Cava Leiomyosarcoma Involving the Renal Veins.

OBJECTIVE: This retrospective study aimed to show the practice of preserving renal function during curative resection of inferior vena cava leiomyosarcoma (IVCL) involving the renal veins at a single institution over a 7 year period. MATERIALS AND METHODS: From February 2009 to February 2017, 10 patients (6 women; median age 49 years) with IVCL involving the renal veins were treated surgically at Peking Union Medical College Hospital. En bloc resections were performed in all patients, and the renal outflows were preserved in eight patients using a new method: venoplasty of the renal ostia (VRO). Data regarding patient details, pre-operative preparation, surgical procedures, post-operative recovery, and follow-up results were obtained and reviewed retrospectively. RESULTS: Computed tomography and intra-operative examinations revealed that renal vein confluences were involved but not invaded in all cases except Patient 4. All patients underwent curative en bloc tumour excision; a right nephrectomy was performed in only one patient (Patient 4) whose tumour invaded the right renal vein. The mean operation time was 358 min and the mean blood loss 1935 mL. At a median follow-up of 54.5 months, the 5 year local recurrence, distant metastasis, overall survival, and disease-free survival rates were 20%, 10%, 68.6%, and 38.1%, respectively. CONCLUSIONS: Venoplasty of the renal ostia is an effective method of preserving the renal veins and reconstructing renal outflow.

Type I IFN induces protein ISGylation to enhance cytokine expression and augments colonic inflammation.

Type I IFNs have broad activity in tissue inflammation and malignant progression that depends on the expression of IFN-stimulated genes (ISGs). ISG15, one such ISG, can form covalent conjugates to many cellular proteins, a process termed "protein ISGylation." Although type I IFNs are involved in multiple inflammatory disorders, the role of protein ISGylation during inflammation has not been evaluated. Here we report that protein ISGylation exacerbates intestinal inflammation and colitis-associated colon cancer in mice. Mechanistically, we demonstrate that protein ISGylation negatively regulates the ubiquitin-proteasome system, leading to increased production of IFN-induced reactive oxygen species (ROS). The increased cellular ROS then enhances LPS-induced activation of p38 MAP kinase and the expression of inflammation-related cytokines in macrophages. Thus our studies reveal a regulatory role for protein ISGylation in colonic inflammation and its related malignant progression, indicating that targeting ubiquitin-activating enzyme E1 homolog has therapeutic potential in treating inflammatory diseases.

Effect of Adequate Anticoagulantion Therapy on the Outcome of Spontaneous Isolated Dissection of Superior Mesenteric Artery.

Objective To investigate the optimal treatment strategy of spontaneous isolated dissection of superior mesenteric artery (SIDSMA) and the effect of anticoagulation therapy on the prognosis of SIDSMA. Methods The clinical data of 29 patients presented with acute or subacute mesenteric ischemia (a history of less than 14 days) due to SIDSMA admitted to the Department of Vascular Surgery of Peking Union Medical College Hospital from January 1st 2003 to December 31th 2016 were retrospectively analyzed. Results In this study,28 cases were male and the remaining one was female,with an average age of (49.1±7.6) years. The emergency endovascular treatment were performed on 4 cases with severe mesenteric intestinal ischemia,and the symptoms were relieved postoperatively. The remaining 25 cases were treated with conservative treatment. Among 13 cases who were received adequate anticoagulantion therapy,symptoms were relieved or disappeared in 9 cases (69.2%),whereas conservative treatment was ineffective in 4 cases (30.8%),for whom surgical intervention were performed. Among 12 cases who received conservative treatment without sufficient anticoagulation,the abdominal pain was relieved in only 2 cases (16.7%) and the remaining 10 cases (83.3%) were converted to surgical intervention. The success rate of conservative treatment for patients with adequate anticoagulant therapy was significantly higher than that of patients who had not received adequate anticoagulant therapy (P=0.015). Conclusions Adequate anticoagulation therapy has good therapeutic effect in most SIDSMA cases with acute or subacute mesenteric ischemia. For patients with severe mesenteric ischemia or those fail to respond to initial conservative treatment,endovascular treatment may be a more reasonable option.

[Interval-spaced Sessions of Partial Splenic Artery Embolization in Juvenile Patients with Hypersplenism].

Objective To determine whether interval-spaced sessions of partial splenic artery embolization(PSE) is a safe and effective alternative treatment for hypersplenism in juvenile patients. Methods Eight patients(3 males and 5 females) were included in this retrospective study.All patients were diagnosed as hypersplenism and underwent PSE in 2-3 sessions separated by 1-2 month intervals.Immediate,short,and long term follow-up were done.The effectiveness of the treatment was evaluated.Results No major postoperative complication was noted.No patient developed septic shock,splenic abscess,or spleen rupture.Postoperative pain and fever were common and manageable;only two patients developed loculated pleural effusions,which were well alleviated after conservative treatment.All patients showed significant increase in thrombocytes and white blood cells count after the first session of embolization.The cell counts became remarkable after the last session and remained at normal levels during the follow-up period.Conclusions PSE using 2-3 interval-spaced sessions can effectively decrease spleen size and reverse hypersplenism in juvenile patients.Also,it may reduce the postoperative complications commonly seen in traditional PSE.

Functions of the 19S complex in proteasomal degradation.

The 26S proteasome degrades ubiquitylated proteins. It consists of the 20S proteasome and the PA700/19S complex. PA700 plays essential roles in processing ubiquitylated substrates; it can bind, deubiquitylate, and unfold ubiquitylated proteins, which then translocate into the proteolytic chamber of the 20S proteasome for degradation. Here, we summarize the current knowledge of PA700-mediated substrate binding and deubiquitylation, and provide models to explain how substrate binding and deubiquitylation could regulate proteasomal degradation. We also discuss the features and potential therapeutic uses of the two recently identified small molecule inhibitors of the proteasome-residing deubiquitylating enzymes.

Endovascular Repair for Acute Type B Aortic Dissection.

Objective To report experience and result of endovascular repair for acute type B aortic dissection (ATBD). Methods Totally 125 ATBD patients receiving endovascular repair with stent-graft were enrolled in this study. Demographic data,operation details,perioperative findings,and follow-up results were retrospectively analyzed. Results All the 125 patients were successfully implanted with 135 stent-grafts. Thirteen cases were covered left subclavian artery,16 cases underwent left subclavian artery revascularization,and 10 cases underwent visceral artery revascularization. No perioperative mortality occurred. Meanwhile,the perioerative major adverse events included renal infarction (n=1),renal artery bleeding (n=2),stroke (n=2),myocardial infarction (n=1),and renal dysfunction (n=2;one of them suffered from permanent dialysis),and incision complication (n=5). The mean cost during hospital stay was (112 657±58 921) Yuan;more specifically,the cost for complicated dissection cases was significantly higher than uncomplicated cases [(171 623±93 635)Yuan vs. (92 531±48 721) Yuan,P<0.001]. All the patients received regular follow-up for 3-120 months [mean (23.5±11.2) months],except that 14 cases (11.2%) lost to follow-up. During the follow-up,three deaths were reported,among whom one died due to rupture of distal dissection one year after primary operation. No re-intervention case was noted. Conclusions Endovascular repair for ATBD is safe and feasible. Emergency repair for complicated ATBD cases can get satisfactory results,although the medical cost is higher than uncomplicated cases.

Impact of the Action Time of Inducers on Differentiation of 3T3-L1 Cells.

Objective To explore the effect of the action time of inducers on the differentiation of 3T3-L1 cells to adipocytes. Methods According to the "Cocktail" method,3T3-L1 cells were divided into three groups according to the action time of inducers,with the action time being 2,3 or 4 days,respectively. Cell morphology was observed using inverted microscope and adipose content were detected by Oil red "O" staining and detection of triglyceride. The cell viability was identified by trypan blue staining method. Results The proportion of samples (n=12) with differentiation rate above 80% in group A was 66% (12/18),while the differentiation rate of all the samples (n=18)in group B and group C were above 80%. For the Oil red "O",the OD value at 510 nm in group C was 2.59±0.17,which was significantly higher than that in group A (2.12±0.47;F=6.62,P=0.0001)and group B (2.20±0.17;F=5.15,P=0.0001),while no significant difference was found between group A and group B (F=1.14,P=0.74). As for the triglyceride,the value in group C was (1351.04±119.01)ng/ml,which was significantly higher than that in group A[ (1077.88±272.75)ng/ml;F=6.73,P=0.001] and group B [(1089.38±115.39)ng/ml;F=5.78,P=0.001],while no difference was found between group A and group B (F=0.27,P=0.64). The cell viability in group A,B,and C was (98.3±1.2)%,(98.5±1.8)%,and (98.9±2.1)%,respectively,showing no significant difference (F=0.18,P=0.83). Conclusions The modified procedure for the differentiation of 3T3-L1 cells to adipocytes can increase the differentiation rate and thus may be applied for establishing adipocyte models. The recommended action time is three days.

Residue histidine 50 plays a key role in protecting α-synuclein from aggregation at physiological pH.

α-Synuclein (αSyn) aggregation is involved in the pathogenesis of Parkinson disease (PD). Recently, substitution of histidine 50 in αSyn with a glutamine, H50Q, was identified as a new familial PD mutant. Here, nuclear magnetic resonance (NMR) studies revealed that the H50Q substitution causes an increase of the flexibility of the C-terminal region. This finding provides direct evidence that this PD-causing mutant can mediate long range effects on the sampling of αSyn conformations. In vitro aggregation assays showed that substitution of His-50 with Gln, Asp, or Ala promotes αSyn aggregation, whereas substitution with the positively charged Arg suppresses αSyn aggregation. Histidine carries a partial positive charge at neutral pH, and so our result suggests that positively charged His-50 plays a role in protecting αSyn from aggregation under physiological conditions.

Multi-stimuli-responsive chiral organogels based on peptide derivatives.

A series of chiral aryl amide compounds bearing peptide pendants have been investigated as low molecular weight gelators. A mechanistic study reveals that complementary hydrogen bonding from peptide pendants is the main driving force for the formation of organogels. This new class of organogels can exhibit multi-stimuli-responsive behavior upon applying (1) thermal, (2) pH, (3) enantiomeric purity, and (4) fluoride anion stimuli. Enantiomeric purity as a new external stimulus displays sensitive stimuli-responsiveness; only 0.02 equiv. of the enantiomer can completely disassemble the gel aggregate. They will serve as excellent smart materials with potential applications in chiral sensors, recognition, and separation.

[Logistic Regression Analysis of Depression in Arteriosclerosis Obliterans Patients and Its Risk Factors].

OBJECTIVE: To investigate the depression in arteriosclerosis obliterans (ASO) patients and its risk factors. METHODS: The self-rating depression scale (SDS) was applied in 228 ASO patients hospitalized in the vascular surgery department of Peking Union Medical College Hospital from March 2010 to October 2011. The risk factors of depression were analyzed by using univariate and multivariate Logistic regression analysis. RESULTS: Of these 228 ASO patients, 133 (58.3%) were found to be depressive. Univariate and multivariate analysis showed that female (OR=0.15,95% CI:0.05-0.45), hypertension (OR=4.63,95% CI:1.90-11.29), coronary heart disease (OR=3.62,95%CI:1.43-9.18), as well as Fontaine 2a (OR=20.76,95% CI:3.21-134.28), 2b (OR=26.34,95% CI:4.20-164.97), 3(OR=192.28,95% CI:25.97-1423.51), and 4(OR=291.41,95% CI:28.67-2962.21) were the risk factors of depression in ASO patients. CONCLUSIONS: ASO patients can easily develop depression. Female, hypertension, coronary heart disease, and Fontaine 2a, 2b,3,and 4 are the risk factors of depression in ASO patients.

Protective effect of melatonin on cigarette smoke-induced restenosis in rat carotid arteries after balloon injury.

Vascular restenosis after the interventional angioplasty remains the main obstacle to a favorable long-term patency. Many researches suggest cigarette smoking is one of the most important causes of restenosis. This study was designed to investigate whether melatonin could protect against the cigarette smoke-induced restenosis in rat carotid arteries after balloon injury. Three groups of male rats (normal condition, cigarette smoke exposed, cigarette smoke exposed, and melatonin injected) were used in this study. An established balloon-induced carotid artery injury was performed, and the carotid arteries were harvested from these three groups 14 days later. The ratio of intima to media, the infiltration of inflammatory cells, the expression of inflammatory cytokines (NF-κB, IL-1ß, IL-6, TNF-α, MCP-1), adhesion molecules (ICAM-1, VCAM-1), and eNOS were measured. The results showed that cigarette smoke exposure aggravated the stenosis of the lumen, promoted the infiltration of inflammatory cells and induced the expression of the inflammatory cytokines and adhesion molecules after the balloon-induced carotid artery injury. Moreover, cigarette smoke exposure can inhibit the expression of eNOS. Particularly, we surprised that melatonin could minimize this effect caused by cigarette smoke. These results suggested that melatonin could prevent the cigarette smoke-induced restenosis in rat carotid arteries after balloon injury and the mechanism of its protective effect may be the inhibition of the inflammatory reaction. This also implies melatonin has the potential therapeutic applicability in prevention of restenosis after the vascular angioplasty in smokers.