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Objective: To investigate the safety and efficacy of a varicose vein sealant kit in the treatment of great saphenous vein dysfunction. Methods: It was a randomized controlled trial. A total of 180 patients with great saphenous vein dysfunction were enrolled prospectively, and scheduled for surgical treatment in 9 hospitals, including the Second Affiliated Hospital of Naval Medical University, Shanghai Oriental Hospital Affiliated to Tongji University, Xuanwu Hospital Capital Medical University, the First Hospital of Hebei Medical University, Ganzhou People's Hospital, Shanxi Bethune Hospital, the Second Affiliated Hospital of Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, and Zhongshan Hospital Affiliated to Xiamen University, from June to October 2022. Using a random number table method, the subjects were divided into an experimental group and a control group, with 90 cases in each group. The patients of experimental group received treatment with varicose vein sealant kit, while the patients of control group received radiofrequency ablation. The main outcome measure was the complete closure rate of the great saphenous vein in both groups of patients 3 months after surgery. The secondary outcome measures were the complete closure rate of the great saphenous vein in both groups of patients immediately after surgery and 6 months after surgery, the operation time for closing the main trunk of the great saphenous vein, pain score, venous clinical severity score (VCSS), Aberdeen varicose veins questionnaire (AVVQ) at different times before and after surgery, and the incidence of complications in both groups of patients. The non inferiority threshold for the two treatment methods is set at "-10.00%". Results: A total of 177 patients were ultimately enrolled. There were 89 cases in the experimental group, including 38 males and 51 females, with a median age [ M ( Q 1 , Q 3 )] of 59.7(49.6, 66.7) years, and 88 cases in the control group, including 30 males and 58 females, with a median age of 57.2(46.9, 65.9) years. A total of 174 patients completed a 3-month follow-up, and 167 patients completed a 6-month follow-up. The closure time of the main saphenous vein in the experimental group was (22.1±11.1) min, which was longer than the control group, which was (18.7±9.8) min ( P =0.031). The complete closure rate of the great saphenous vein immediately after surgery in both the experimental group and the control group was 100%. The complete closure rates of the great saphenous vein at 3 months after surgery were 98.8% (85/86) and 98.9% (87/88), respectively. The lower limit of the 95% CI for the difference between the two groups was -3.19%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P <0.001). The complete closure rates of the great saphenous vein at 6 months after surgery were 97.6% (81/83) and 100% (84/84), the lower limit of the 95% CI for the difference between the two groups was -5.71%, which was greater than the non-inferiority threshold of -10.00% (non-inferiority P <0.001). The immediate pain scores after complete anesthesia awakening of the experimental group and the control group were both 1.0 (0, 2.0), with no statistically significant difference ( P =0.365). The incidence of bruising in the experimental group and the control group one week after surgery was 61.2% (52/85) and 67.1% (57/85), respectively, with no statistically significant difference ( P =0.181). There was no statistically significant difference in VCSS and AVVQ scores between groups before surgery and at 1, 3, and 6 months after surgery (all P >0.05). There was no statistically significant difference in the incidence of complications such as deep vein thrombosis, phlebitis, pain, and subcutaneous hematoma in the lower limbs 3 months after surgery (all P >0.05). Conclusion: The varicose vein sealant kit is safe and effective in treating great saphenous vein dysfunction, and can achieve a complete closure rate of great saphenous vein that is not inferior to traditional radiofrequency ablation.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD + loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD + loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases., (© 2024. The Author(s).)

Objective: To analyze the contents of different kinds of fatty acids in carotid atherosclerotic plaques. Methods: A total of 24 patients who underwent carotid endarterectomy at the Second Affiliated Hospital of Naval Medical University from October 2021 to September 2022 due to moderate and severe carotid artery stenosis were retrospectively enrolled, including 20 males and 4 females, with a median age[ M ( Q 1 , Q 3 )] of 68.5 (63.5, 72.3) years. According to the symptoms of cerebral ischemia, the patients were divided into a symptomatic group (12 cases) and an asymptomatic group (12 cases). Regarding the pathological characteristics, the patients were divided into a stable group (14 cases) and a vulnerable group (10 cases) according to carotid plaque pathology scores. The expression differences of different types of fatty acids in carotid plaques were analyzed by targeted fatty acid metabolomics technology based on ultra-performance liquid chromatography-mass spectrometry (UPLC-ESI-MS/MS) analysis. Results: In the 24 samples, the median amount of fatty acids [ M ( Q 1 , Q 3 )] was 1 113 (330, 5 897) ng/g. A total of 13 medium and long-chain fatty acids were detected, including saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. The content of saturated fatty acids was 584 (290, 9 888) ng/g, accounting for the highest proportion of 51.8%. The content of polyunsaturated fatty acids was 1 444 (393, 4 264) ng/g, accounting for 44.4%. The content of monounsaturated fatty acids was 2 793 (1 558, 3 247) ng/g, accounting for 3.8%. The contents of linoleic acid, α-linolenic acid and oleic acid in carotid plaques in the symptomatic group were 1 760 (581, 3 006), 682 (527, 886) and 2 081 (1 358, 2 907) ng/g, respectively, which were lower than those in the asymptomatic group 3 149 (2 226, 4 683), 1 423 (964, 2 270) and 3 178 (2 352, 3 993) ng/g (all P <0.05). The contents of linoleic acid, α-linolenic acid and oleic acid in carotid plaques in the vulnerable group were 1 537 (588, 2 921), 649 (477, 850) and 2 081 (1 129, 2 831) ng/g, respectively, which were lower than those in the stable group 3 149 (2 047, 4 416), 1 423 (940, 2 184) and 3 091 (2 201, 3 973) ng/g (all P <0.05). There were no significant differences in the contents of 11, 14-eicosadienoic acid, γ-linolenic acid, eicosapentaenoic acid, arachidonic acid, erucic acid, margaric acid, pentadecanoic acid, stearic acid, dodecanoic acid and palmitic acid (all P >0.05). Conclusions: Saturated fatty acids are the main type in carotid plaques. The contents of oleic acid, α-linolenic acid and linoleic acid decrease in vulnerable plaques.

Atherosclerotic plaques belong to the common vascular disease in the aged, which rupture will lead to acute thromboembolic diseases, the leading cause of fatal cardiovascular events. Accumulating evidence indicates that the lncRNAs-miRNAs-mRNA regulatory network plays a critical role in atherosclerosis. Based on RNA sequencing (GSE207252), we constructed expression profiles of lncRNAs, microRNAs, and mRNA in the carotid plaque of atherosclerosis patients and analyzed differentially expressed genes (DEGs). We identified three candidate lncRNAs using two algorithms (LASSO and SVM-RFE): lnc&#95;GLRX3, lnc&#95;FGF7-5, and DISC1FP1). LNCipedia, TargetScan, and miRDB databases were used to predict target miRNAs of lncRNAs and target genes of miRNAs. Gene ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA) analysis of DEGs was carried out using the R package clusterProfiler. A PPI network was constructed using the STRING website and visualized by Cytoscape. According to the "MCC" method of the plug-in cytoHubba in Cytoscape, ERCC4 was the top hub gene of the PPI network. We constructed a lncRNA&#95;FGF7-5/lncRNA&#95;GLRX3-miR-2681-5p-ERCC4 regulatory network for carotid plaque using lncRNA-miRNA and miRNA-mRNA pairs. Next, lncRNA&#95;FGF7-5 and lncRNA&#95;GLRX3 targeted miR-2681-5p directly to upregulate ERCC4 expression. Silencing of lncRNA&#95;FGF7-5 and lncRNA&#95;GLRX3 promoted apoptosis and TP53 expression in HUVECs treated with ox-LDL; however, these effects were reversed by ERCC4-overexpression. Taken together, these findings indicated that lncRNA&#95;FGF7-5 and lncRNA&#95;GLRX3 together reduced atherosclerosis-induced apoptosis of HUVECs via targeting miR-2681-5p to increase ERCC4 expression, thereby preventing the formation of carotid plaque and finally inhibiting atherosclerosis progression.

Neointima formation is characterized by the proliferation of vascular smooth muscle cells (VSMC). Although lysine-specific demethylase 1 (LSD1) has critical functions in several diseases, its role in neointima formation remains to be clarified. In this study, we aimed to explore the crucial role of LSD1 on neointima formation using a carotid artery injury model in mice. We observed that aberrant LSD1 expression was increased in human and mouse stenotic arteries and platelet-derived growth factor-BB (PDGF-BB)-treated VSMC. Furthermore, LSD1 knockdown significantly mitigated neointima formation in vivo and inhibited PDGF-BB-induced VSMC proliferation in vitro. We further uncovered that LSD1 overexpression exhibited opposite phenotypes in vivo and in vitro. Finally, LSD1 knockdown inhibited VSMC proliferation by increasing p21 expression, which is associated with LSD1 mediated di-methylated histone H3 on lysine 4 (H3K4me2) modification. Taken together, our data suggest that LSD1 may be a potential therapeutic target for the treatment of neointima formation., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the value of color Doppler ultrasound and digital subtraction angiography (DSA) in evaluating the level of carotid bifurcation and the morphology of extracranial internal carotid artery in patients with atherosclerotic carotid stenosis. Methods: The carotid artery examination data of 186 patients with atherosclerotic carotid stenosis who underwent carotid DSA and color Doppler ultrasound in Shanghai Changzheng Hospital from July 2017 to June 2019 were retrospectively analyzed, including 154 males and 32 females, with ages ranging from 36 to 84 (66±8) years old. The correlation between the position of carotid bifurcation and the level of cervical spine, the distance from the position of carotid bifurcation to mandibular angle, the correlation of the level of bifurcation with the length of neck, and the incidence of carotid distortion were analyzed. Results: DSA showed that the most common position of carotid bifurcation was at C3 level on the left [37.3% (56/150)], and at C3-C4 level on the right [33.6% (42/125)], and the highest position was at C2 level on the left, and at C2-C3 levels on the right, while the lowest level on both sides was at C5 level. The incidence of high bifurcation of left carotid artery (C3 and above) was 46% (69/150), which was higher than that of right carotid artery [21.6% (27/125), P <0.001]. The incidence of high carotid bifurcation in men and women was 33.2% (76/229) and 43.5% (20/46), respectively, with no significant difference ( P = 0.182). Carotid ultrasound showed that the distance between the left carotid bifurcation and the mandibular angle was (3.0±1.3) cm, which was shorter than that on the right [(3.4±1.2) cm] ( P <0.001). The distance between carotid bifurcation and mandibular angle in men and women was (3.2±1.2) cm and (3.3±1.0) cm, respectively, with no significant difference ( P = 0.093). There was no significant correlation between carotid bifurcation level and carotid length (right: r = 0.02, P = 0.091; left: r = 0.01, P = 0.927). The incidence of carotid artery distortion was 28.1% (9/32) in women and 15.6% (24/154) in men, with no significant difference ( P = 0.091). The incidence of right carotid artery distortion in high bifurcation group was 59.3% (16/27), which was higher than that in non-high bifurcation group [3.1% (3/98)] ( P <0.001). Likewise, the incidence of left carotid artery distortion in high bifurcation group was 30.4% (21/69), which was higher than that in non-high bifurcation group [2.5% (2/81)] ( P< 0.001). Conclusions: The bifurcation position of left carotid artery in patients with atherosclerotic carotid stenosis is higher than that of the right. Patients with high bifurcation of carotid artery are more likely to be complicated with carotid distortion. Preoperative color doppler ultrasound combined with DSA can evaluate the distortion of extracranial carotid artery, thereby providing reference for the selection of surgical methods.

Objective: To summarize the classification and clinical treatment experience of cervical massive hemorrhage in multiple centers. Methods: From April 2012 to October 2020, clinical data of 42 patients with cervical massive hemorrhage were retrospectively analyzed, including 27 cases from Shanghai Changzheng Hospital, 7 cases from Hunan Provincial People's Hospital, 4 cases from Longkou People's Hospital and 4 cases from Laizhou People's Hospital. According to bleeding position (P), bleeding vessel (V), cerebral blood supply (C), and the presence or absence of associated injury (A), 42 patients were classified as "PVCA", and summarize the methods of pre-hospital emergency and in-hospital treatment based on the "ABC" treatment principles: airway rebuild (A), effective arterial hemostasis and bleeding stop (B), and cerebral blood flow reconstruction within the time window (C). Results: Within the 42 cases of cervical massive hemorrhage, there were 3 cases of type P1 (below cricoid cartilage), 28 cases of type P2 (cricoid cartilage-mandibular angle), 11 cases of type P3 (mandibular angle-skull base); 22 cases of type V1 (arterial hemorrhage), 11 cases of type V2 (main venous hemorrhage), 7 cases of type V3 (simple superficial vein or small artery hemorrhage), 2 cases of type V4 (mixed arteriovenous hemorrhage); 5 cases of type C0 (no symptoms of cerebral ischemia and neurological dysfunction), 33 cases of type C1 (transient cerebral ischemia without sensory disturbance), 4 cases of type C2 (symptoms of cerebral ischemia and neurological dysfunction); 39 cases of type A0 (no other system damage was involved) and 3 cases of type A1 (combined with other system damage). All 42 patients received operations, 25 patients received open surgery of vascular reconstruction+hematoma/foreign body removal (7 cases of vascular ligation, 14 cases of direct suture repair, 4 cases of vascular interposition), 17 patients received hybrid surgery (carotid angiography+covered stent repair+hematoma/foreign body removal). The surgical technique success rate the was 100%. All the hemorrhagic shock was corrected, hematoma compression was relieved, and the symptoms of cephalic ischemia were improved. There were 4 cases of local cranial nerve injury, 1 case of incision hematoma and 6 cases of postoperative hyper perfusion. During the average 14.3 months follow-up, there was no operation related myocardial infarction, stroke or death, no re-rupture or re-dissection, and 50% asymptomatic restenosis was found in 1 case one year after received covered stent endovascular repair. Conclusion: Based on the "PVCA" classification and "ABC" treatment principle, it is safe and effective to rescue cervical massive hemorrhage.

Neck is an important and complex region of the human body. Once injury occurs, it often leads to a high mortality rate and complication rate, among which vascular injury and massive hemorrhage are the main causes. However, due to the particularity of neck structure, there is a lack of effective control methods for cervical vascular hemorrhage, and there is still no consensus on the diagnosis and treatment of cervical vascular hemorrhage. Combined with the newest researches, this paper tries to explore and summarize the experience of the new classification and management principle of vascular massive hemorrhage.

Rationale: SNX10 (sorting nexin 10) has been reported to play a critical role in regulating macrophage function and lipid metabolism., Objective: To investigate the precise role of SNX10 in atherosclerotic diseases and the underlying mechanisms., Methods and Results: SNX10 expression was compared between human healthy vessels and carotid atherosclerotic plaques. Myeloid cell-specific SNX10 knockdown mice were crossed onto the APOE -/- (apolipoprotein E) background and atherogenesis (high-cholesterol diet-induced) was monitored for 16 weeks. We found that SNX10 expression was increased in atherosclerotic lesions of aortic specimens from humans and APOE -/- mice. Myeloid cell-specific SNX10 deficiency (Δ knockout [KO]) attenuated atherosclerosis progression in APOE -/- mice. The population of anti-inflammatory monocytes/macrophages was increased in the peripheral blood and atherosclerotic lesions of ΔKO mice. In vitro experiments showed that SNX10 deficiency-inhibited foam cell formation through interrupting the internalization of CD36, which requires the interaction of SNX10 and Lyn-AKT (protein kinase B). The reduced Lyn-AKT activation by SNX10 deficiency promoted the nuclear translocation of TFEB (transcription factor EB), thereby enhanced lysosomal biogenesis and LAL (lysosomal acid lipase) activity, resulting in an increase of free fatty acids to fuel mitochondrial fatty acid oxidation. This further promoted the reprogramming of macrophages and shifted toward the anti-inflammatory phenotype., Conclusions: Our data demonstrate for the first time that SNX10 plays a crucial role in diet-induced atherogenesis via the previously unknown link between the Lyn-Akt-TFEB signaling pathway and macrophage reprogramming, suggest that SNX10 may be a potentially promising therapeutic target for atherosclerosis treatment.

Objective: To investigate the surgical indications, preoperative evaluation, technical points, perioperative management and effect of transcarotid artery revascularization (TCAR) in the treatment of carotid stenosis. Methods: From March to April 2019, three patients with carotid stenosis undergoing TCAR in the Second Affiliated Hospital of Naval Military Medical University. With the common carotid artery approach, under the protection of the carotid-femoral vein reverse blood flow, the balloon dilatation of the internal carotid artery stenosis and stent implantation to achieve the purpose of carotid revascularization.The patient's general condition, preoperative evaluation, intraoperative operation, postoperative management and complications were recorded in detail. The clinical safety, efficacy and efficacy of TCAR in the treatment of carotid stenosis were evaluated. Results: All three operations were successful, including 2 cases of left carotid artery revascularization and 1 case of right carotid artery revascularization. A total of 3 carotid stents were implanted. The operation time was 65, 59, and 55 min,the intraluminal operation time was 13, 18, and 11 min, the common carotid artery blocked time was 15, 20, and 13 min, the contrast agent was 20, 25,15 ml, respectively. There was no death, no nervous system and other related complications during the perioperative period. Three patients were followed up for 7, 7, and 6 months without death, there were no nervous system diseases and other complications. All patients with ultrasound indicated that the carotid artery stent was patency. Conclusion: TCAR adopts the neuroprotection system of carotid-femoral vein continuous reverse blood flow to prevent transient ischemic attack (TIA) and stroke, and it is a safe and effective treatment for carotid artery stenosis.

Objective: To evaluate the safety and efficacy of carotid endarterectomy (CEA) and carotid angioplasty with stenting(CAS) for carotid artery stenosis after radiotherapy. Methods: The clinical data of 73 cases with carotid artery stenosis after radiotherapy from October 2007 to September 2017 were analyzed retrospectively. Among them, 36 cases underwent CEA and 37 cases underwent CAS. Results: No complications occurred during the perioperative period in both groups. During the follow-up period, transient cerebral ischemia occurred in 1 case in the CEA group. There was no in-stent restenosis or adverse events such as stroke or myocardial infarction. In the CAS group, transient cerebral ischemia occurred in 2 cases, postoperative restenosis occurred in 2 cases, and myocardial infarction occurred in 1 case. The restenosis rate and incidence of adverse events were lower in the CEA group. Conclusions: Both surgical methods are safe and effective in the treatment of carotid artery stenosis after radiotherapy. CEA surgery can be more beneficial to long-term outcome, and it is supposed to be the preferred surgical method.

Objective: To explore a modified method for constructing a mouse model of instable carotid plaque and provide the mouse model for simulating the development of human instable carotid plaque. Methods: Twenty-four low density lipoprotein receptor deficiency (LDLr-/-), C57BL/6, male mice were randomized into two groups according to computer-generated table, tandem constriction of carotid artery+ high cholesterol diet (tandem surgery group, n= 12); sham surgery+ high cholesterol diet(sham surgery group, n= 12). After 12 weeks of consecutive feeding, murine carotid artery were collected and analyzed by carotid ultrasound, pathological examination to assess the formation and stability of atherosclerotic plaque. Results: No statistical difference in body weight and blood lipid level between the two groups was observed (all P> 0.05). After surgery, through ultrasound biomicroscopy, obvious stenosis at the two sites of tandem constriction and atherosclerotic plaque between the two sites were observed in tandem surgery group. By pathological examination, no plaque was formed in carotid artery in sham surgery group. The lipid area in the stable plaque of innominate artery in sham surgery group and the plaque of carotid artery in tandem surgery group were (4.8±0.6) ×10(4),(10.2±1.1)×10(4) μm(2), respectively. The difference was statistically significant between the two groups ( t= 12.023, P< 0.001). In addition, the thickness of fibrous cap in the above groups were (122.4±17.8), (41.3±20.2) μm, respectively. The difference was statistically significant either ( t= 9.224, P< 0.001). The region of necrotic core were (3.3±0.4)×10(4),(8.1±0.9)×10(4) μm(2).The difference was statistically significant as well ( t= 13.456, P< 0.001). The percentage of macrophages in innominate artery of sham surgery group and in carotid artery of tandem surgery group were (20.8±5.2)%, (38.6±6.4)%, respectively.The percentage of vascular smooth muscle cells were (32.5±7.3)%,(21.2±5.1)%, respectively ( t= 6.114,3.585, all P< 0.05). The results indicated that the plaque in tandem surgery group had severer inflammatory response. Conclusion: Through tandem constriction surgery upon carotid artery in LDL-/-mouse, instable carotid atherosclerotic plaque can be induced, which is less time-consuming, replicable and effective.

Neointimal hyperplasia as a consequence of vascular injury is aggravated by inflammatory reaction and oxidative stress. The α7 nicotinic acetylcholine receptor (α7nAChR) is a orchestrator of cholinergic anti-inflammatory pathway (CAP), which refers to a physiological neuro-immune mechanism that restricts inflammation. Here, we investigated the potential role of CAP in neointimal hyperplasia using α7nAChR knockout (KO) mice. Male α7nAChR-KO mice and their wild-type control mice (WT) were subjected to wire injury in left common carotid artery. At 4 weeks post injury, the injured aortae were isolated for examination. The neointimal hyperplasia after wire injury was significantly aggravated in α7nAChR-KO mice compared with WT mice. The α7nAChR-KO mice had increased collagen contents and vascular smooth muscle cells (VSMCs) amount. Moreover, the inflammation was significantly enhanced in the neointima of α7nAChR-KO mice relative to WT mice, evidenced by the increased expression of tumor necrosis factor-α/interleukin-1β, and macrophage infiltration. Meanwhile, the chemokines chemokine (C-C motif) ligand 2 and chemokine (CXC motif) ligand 2 expression was also augmented in the neointima of α7nAChR-KO mice compared with WT mice. Additionally, the depletion of superoxide dismutase (SOD) and reduced glutathione (GSH), and the upregulation of 3-nitrotyrosine, malondialdehyde and myeloperoxidase were more pronounced in neointima of α7nAChR-KO mice compared with WT mice. Accordingly, the protein expression of NADPH oxidase 1 (Nox1), Nox2 and Nox4, was also higher in neointima of α7nAChR-KO mice compared with WT mice. Finally, pharmacologically activation of CAP with a selective α7nAChR agonist PNU-282987, significantly reduced neointima formation, arterial inflammation and oxidative stress after vascular injury in C57BL/6 mice. In conclusion, our results demonstrate that α7nAChR-mediated CAP is a neuro-physiological mechanism that inhibits neointima formation after vascular injury via suppressing arterial inflammation and oxidative stress. Further, these results imply that targeting α7nAChR may be a promising interventional strategy for in-stent stenosis., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Irisin is a novel exercise-induced myokine involved in the regulation of adipose browning and thermogenesis. In this study, we investigated the potential role of irisin in cerebral ischemia and determined whether irisin is involved in the neuroprotective effect of physical exercise in mice., Materials and Methods: The middle cerebral artery occlusion (MCAO) model was used to produce cerebral ischemia in mice. First, the plasma irisin levels and changes in expression of the irisin precursor protein FNDC5 in skeletal muscle were determined post ischemic stroke. Second, the association between plasma irisin levels and the neurological deficit score, brain infarct volume, or plasma concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in mice with MCAO were evaluated. Third, the therapeutic effect of irisin on ischemic brain injury was evaluated in vivo and in vitro. Recombinant irisin was injected directly into the tail vein 30min after the MCAO operation, and then the effects of irisin treatment on brain infarct volume, neurological deficit, neuroinflammation, microglia activation, monocyte infiltration, oxidative stress and intracellular signaling pathway activation (Akt and ERK1/2) were measured. Irisin was also administered in cultured PC12 neuronal cells with oxygen and glucose deprivation (OGD). Finally, to assess the potential involvement of irisin in the neuroprotection of physical exercise, mice were exercised for 2weeks and an irisin neutralizing antibody was injected into these mice to block irisin 1h before the MCAO operation., Results: The plasma irisin concentration and intramuscular FNDC5 protein expression decreased after ischemic stroke. Plasma irisin levels were negatively associated with brain infarct volume, the neurological deficit score, plasma TNF-α and plasma IL-6 concentrations. In OGD neuronal cells, irisin protected against cell injury. In mice with MCAO, irisin treatment reduced the brain infarct volume, neurological deficits, brain edema and the decline in body weight. Irisin treatment inhibited activation of Iba-1 + microglia, infiltration of MPO-1 + monocytes and expression of both TNF-α and IL-6 mRNA. Irisin significantly suppressed the levels of nitrotyrosine, superoxide anion and 4-hydroxynonenal (4-HNE) in peri-infarct brain tissues. Irisin treatment increased Akt and ERK1/2 phosphorylation, while blockade of Akt and ERK1/2 by specific inhibitors reduced the neuroprotective effects of irisin. Finally, the exercised mice injected with irisin neutralizing antibody displayed more severe neuronal injury than the exercised mice injected with control IgG., Conclusion: Irisin reduces ischemia-induced neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotective effect of physical exercise against cerebral ischemia, suggesting that irisin may be a factor linking metabolism and cardio-cerebrovascular diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Transforming growth factor-β (TGF-β)/Smad signaling has been implicated in connective tissue growth factor (CTGF) expression in vascular smooth muscle cells (VSMC). Reactive oxygen species (ROS) are involved in activation of TGF-β/Smad signaling. However, detailed mechanisms underlying the process remain unclear. In present study, we demonstrated TGF-β1 strongly induced CTGF expression, Smad3 activation, NADPH oxidase 4 (Nox4) expression and increased ROS production in primary rat VSMC in vitro. NADPH oxidases inhibitor diphenylene iodonium (DPI) eliminated TGF-β1-induced CTGF expression and ROS generation. In addition, small-interfering RNA (siRNA) silencing of Smad3 or Nox4 significantly suppressed TGF-β1-mediated CTGF expression in VSMC. Furthermore, Nox4 silencing or inhibition eliminated TGF-β1-induced Smad3 activation and interaction between Nox4 and Smad3. In vivo studies further identified a positive correlation of Nox4 levels with Smad3 activation and CTGF expression in atherosclerotic arteries of patients and animal models. These data established that a novel mechanistic link of Nox4-dependent activation of Smad3 to increased TGF-β1-induced CTGF in the process of vascular remodeling, which suggested a new potential pathway for therapeutic interventions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Our study aimed to investigate effect of expressions of tumor necrosis factor α (TNF-α) and interleukin 1B (IL-1B) on peritoneal metastasis of gastric cancer (GC). From June 2012 to June 2014, a total of 60 patients with advanced peritoneal metastasis from GC were collected from Department of Gastrointestinal and Nutriology Surgery at Shengjing Hospital of China Medical University. Furthermore, 60 GC patients without peritoneal metastasis were enrolled as controls. Immunohistochemistry was performed to test TNF-α and IL-1B expression, and logistic regression analysis was employed for evaluating risk factors for peritoneal metastasis of GC. Our results showed that TNF-α expression in metastatic group and non-metastatic group was significantly different (P = 0.043), but no significant difference was found in IL-1B expression between two groups (P = 0.261). In addition, TNF-α expression in metastatic group and non-metastatic group was associated with tumor size, depth of invasion, the degree of differentiation (all P < 0.05). Logistic regression analysis indicated that tumor size, depth of invasion, the degree of differentiation and TNF-α expression were risk factors for peritoneal metastasis of GC (all P < 0.05). Our study found that TNF-α expression may play a vital role in peritoneal metastasis of GC, while IL-1B expression might not be correlated with peritoneal metastasis.

Background: Multilayer stent has become a new endovascular strategy for visceral artery aneurysm repair. However, its use was not allowed in some areas, such as China. This study evaluates an alternative method: multiple overlapping bare stents for repairing visceral artery aneurysms., Methods: Twenty-four patients with celiac artery aneurysm (n = 2), splenic artery aneurysm (n = 8), hepatic artery aneurysm (n = 3), superior mesenteric artery aneurysm (n = 6), and renal artery aneurysm (n = 5) were treated with 2 to 4 overlapping bare stents. Long-term results, including clinical achievement ratio and target artery patency, were followed up with computed tomographic angiography., Results: Insertion of overlapping bare stents was successful in all patients. Five aneurysms (21%) were totally excluded 3 months after operation, increasing to 12 (50%) and 20 (83%) aneurysms with total isolation at 6 and 12 months' follow-up, respectively. The clinical achievement ratios of multiple overlapping bare stents on splenic artery aneurysms, hepatic artery aneurysms, renal artery aneurysms, celiac artery aneurysms, and superior mesenteric artery aneurysms were 75%, 100%, 80%, 50%, and 100%, respectively. All cases combined had 100% target artery patency., Conclusions: Preliminary experience showed that repair using multiple overlapping bare stents seemed to be a potential alternative strategy for treating visceral artery aneurysm, resulting in target artery patency. However, the exact mechanism requires further study and more cases should be involved., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To clarify the outcome of surgical reconstruction for renal artery in Takayasu arteritis-induced renal artery stenosis (TARAS)., Methods: A retrospective chart review was conducted on 33 consecutive patients with TARAS, who underwent aortorenal bypass (ARB) with autologous saphenous vein graft. There were 9 male and 24 female patients, with a mean age of (25 ± 11) years. The effects on blood pressure and renal function were analyzed. Primary, primary assisted, and secondary patency rates were determined. The effects of various factors on primary patency rate were analyzed. All patients showed hypertension. The mean blood pressure was (175 ± 26)/(100 ± 19) mmHg (1 mmHg = 0.133 kPa). The mean antihypertensive dosage was (2.1 ± 0.6) defined daily dose (DDD). Seventeen patients showed intractable hypertension. Mean estimated glomerular filtration rate was (78 ± 5) ml/min. One patient was dialysis-dependent, and 3 patients were combined with congestive heart failure., Results: ARB was performed for the 39 renal arteries, including 27 unilateral and 6 bilateral bypasses. Postoperative morbidity was 15.2%. All patients survived. During follow-up of mean (56 ± 18) months, two graft occlusions and four graft restenoses occurred. All graft restenoses were eliminated successfully with percutaneous angioplasty, but one patient experienced restenosis again six months later. At 1, 3, and 5 years of follow-up, primary patency was 92%, 89%, and 79%, respectively, primary assisted patency was 95%, 95%, and 91%, respectively, and secondary patency was 95%, 95%, and 91%, respectively. ARB resulted in a decrease in mean blood pressure to 139/85 mmHg (one month post-ARB, P = 0.000) and 136/80 mmHg (last follow-up, P = 0.000), and a reduction in mean antihypertensive dosage to 1.4 DDD (one month post-ARB, P = 0.084) and 0.6 DDD (last follow-up, P = 0.000). Mean estimated glomerular filtration rate increased to 82 ml/min (P = 0.458) one month post-ARB, and 91 ml/min (P = 0.044) at last follow-up, respectively. The dialysis-dependent patient no longer required hemodialysis, and left ventricular dysfunction resolved in all of the three patients., Conclusion: ARB using the autologous saphenous vein graft is safe, effective and durable for treating TARAS.

Objective: To evaluate the effect of the diameter of abdominal aortic aneurysm (AAA) on endovascular exclusion (EVE) and its results., Methods: From March 1997 to June 2007, 429 AAA patients were treated with endovascular stent-graft exclusion. According to the maximal diameter of abdominal aortic aneurysm, the patients were divided into two groups: group A (diameter < 55 mm, n = 274) and group B (diameter > or = 55 mm, n = 155). The diameter of AAA, involvement of iliac artery, length, diameter and distortion of aneurismal neck in the two groups were recorded and compared retrospectively., Results: Patients in group B were significantly older than group A (73.7 vs 71.1 years, P < 0.05). More patients in group B was complicated with coronary artery disease than those in group A (P < 0.05). The mean diameter of AAA in group A was (46.6 +/- 6.8) mm, and (66.8 +/- 11.2) mm in group B (P < 0.05). Proximal aneurysmal necks were shorter, wider and more tortuous in group B than those in group A (P < 0.05). Extraperitoneal approach, embolism of inner iliac artery and reconstruction of another inner iliac artery and stretch technique were more applied in group B. There were more endoleak during operation in group B and more stent-grafts were used. There was significant difference in morbidity rate between the two groups, while no statistic difference in mortality. And in group B, there were a high rate of endoleak and secondary intervention post operation., Conclusions: The diameter of AAA affects EVE and its results. In small aneurysms, EVE carries better outcome than in big aneurysms.

TCM viscera-state theory is an important component of TCM basal theories, accurate English translation of viscera-state terminology is directly related with correct and comprehensive understanding of overseas scholars for TCM visceral functional activities. In the past 30 years, TCM propagation in overseas makes the translation level has increase of a quite degree, but English translation of viscera-state terminology still has some problems to be discussed and improved. In the present paper, the author gives examples to illustrate some problems in English translation of viscera-state terminology and puts forward own opinions to improve the translation from changes of ancient and today terms, textual research of visceral functions and investigation of clinical diseases and syndromes, etc..

Aim: To classify the genes responsible for apoptosis in QGY-7703 cells induced by homoharringtonine (HHT)., Methods: Apoptosis in QGY-7703 cells induced by HHT was demonstrated by DNA fragmentation and morphological observation. cDNA microarray technology was used to detect gene transcription, and the result of microarrays for genes was confirmed by RT-PCR., Results: Seventy-eight individual mRNA were identified and their transcription levels changed significantly. Those genes, of which 68% were upregulated and 32% were downregulated, were partially related to apoptosis. They were mostly oncogenes, tumor suppressors, enzymes, and kinases., Conclusion: HHT is a potential drug in the treatment of liver cancer. TGF-beta, TNF, FAS, p38MAPK, and p53 apoptosis signaling pathways were activated during apoptosis in QGY-7703 cells. Such inducible genes may play important roles in apoptosis and deserve to be further studied.

Chinese meaning and English translation of Jing, Luo, Mai, Jingluo, Jingmai and other terminology of Chinese medicine are compared from both writing and medical theory, raising that the Jingmai in the Internal Classic should include both the channel system and the vessel system. From the form of the characters or functions and structures, the Jing is longitude and the Luo is net, Mai is vessels, and the concept and function of Jingluo (channels and collaterals) and Jingmai (the meridians and vessels) do not allow obscure. In ancient times, Jing and Mai were jointly called as Jingmai, aimed at understanding network state of the channels and collateral system through tangible distribution of the vesselar system. Translation of "Jing mai" as the meridians and collaterals or channels and collaterals practically is only translated a half of real meaning of Jingmai.

Aim: To identify genes responsive to apoptosis in HL-60 cells treated by homoharringtonine., Methods: cDNA microarray technology was used to detect gene expression and the result of microarrays for genes (TIEG and VDUP1) was confirmed by Northern analysis., Results: Seventy-five individual mRNAs whose mass changed significantly were identified. Among these genes (25 were up-regulated and 50 were down-regulated), most are known related to oncogenes and tumor suppressor. Some genes were involved in apoptosis signaling pathways., Conclusion: TGF beta and TNF apoptosis signaling pathways were initiated during apoptosis in HL-60 cells. TIEG and VDUP1 play important roles in mediating apoptosis.

Objective: To assess the operation indications, preoperative evaluation, technique essentials and clinical prospect of endovascular stent-graft exclusion for aortic dissection., Methods: From September 1998 to April 2003, endovascular stent-graft exclusion for aortic dissection (Stanford B) was preformed in 146 patients. CTA or MRA were used as preoperative evaluation methods. Graft was constructed from self-expanding Z-stents covered with a woven Dacron polyester fabric graft (Talent). The stent-grafts were inserted from the femoral or iliac artery to exclude the tear of dissection, and all operations were performed under DSA guidance., Results: The grafts were installed successfully in 145 patients. In 119 patients only proximal tears were excluded, and 26 patients who had both the proximal and distal tears were excluded. The mean follow-up period was 16 months (1 - 54 months). Six patients died within the perioperative period, 2 patients died during the follow-up, 2 patients had recurrence of aortic dissection (Stanford A) and cured by Bentall operation. The others were in good state. No accidents related to the dissection and operation occurred., Conclusions: Endovascular graft exclusion may be a safe and effective treatment for selected patients with thoracic aortic dissection. Endoleak may lead to aneurysmal expansion and rupture. Further follow-up is necessary to evaluate its long-term effect.