[Clinical Effect of Surgical Reconstruction of Extracranial Vertebral Artery].

Objective To evaluate the effect of surgical reconstruction of extracranial vertebral artery and to summarize the experience. Methods The clinical data of 15 patients undergoing surgical reconstruction of extracranial vertebral artery from September 2018 to June 2022 were collected.The operation methods,operation duration,intraoperative blood loss,operation complications,and relief of symptoms were retrospectively analyzed. Results Eleven patients underwent vertebral artery (V1 segment) to common carotid artery transposition,two patients underwent endarterectomy of V1 segment,two patients underwent V3 segment to external carotid artery bypass or transposition.The operation duration,intraoperative blood loss,and blocking time of common carotid artery varied within 120-340 min,50-300 ml,and 12-25 min,with the medians of 240 min,100 ml,and 16 min,respectively.There was no cardiac accident,cerebral hyperperfusion syndrome,cerebral hemorrhage or lymphatic leakage during the perioperative period.One patient suffered from cerebral infarction and three patients suffered from incomplete Horner's syndrome after the operation.During the follow-up (4-45 months,median of 26 months),there was no anastomotic stenosis,new cerebral infarction or cerebral ischemia. Conclusion Surgical reconstruction of extracranial vertebral artery is safe and effective,and individualized reconstruction strategy should be adopted according to different conditions.

Sophocarpine Alleviates Injury-Induced Intima Hyperplasia of Carotid Arteries by Suppressing Inflammation in a Rat Model.

INTRODUCTION: Balloon angioplasty is a commonly applied procedure for treating atherosclerotic vascular diseases. However, the maintenance of long-term lumen patency is relatively difficult due to the occurrence of restenosis. Previous research has shown that the occurrence of vascular wall inflammation is associated with higher rates of restenosis. Sophocarpine (SPC) can exert various therapeutic effects such as anti-oxidation, anti-inflammation, anti-tumor, antivirus and immune regulation. This study aimed to investigate whether SPC can alleviate intimal hyperplasia following balloon injury in a rat carotid artery model. METHODS: Twenty Sprague-Dawley rats were randomly assigned to four groups: (i) control, (ii) balloon injury, (iii) balloon injury followed by saline injection, and (iv) balloon injury followed by SPC administration. Each group contained five rats. A high-pressure balloon of 3 mm × 20 mm was placed in the carotid artery. The balloon was inflated to a pressure of 8 atmospheres to carry out rat carotid artery balloon injury model. The areas of neointimal and media were determined by Verhoeff_Van Gieson staining, and the intima-to-media (I:M) ratios were subsequently evaluated. After that, the protein levels of IL-6, IL-1ß, MCP-1, NF-κB, TNF-α, VCAM-1, ICAM-1 and eNOS were measured. RESULTS: The ratio of I:M was remarkably higher in the balloon injury group than in the control group (p < 0.01). SPC could significantly decrease the ratio of I:M compared with the balloon injury group (p < 0.01). Besides, the protein levels of IL-6, IL-1ß, MCP-1, NF-κB, TNF-α, ICAM-1 and VCAM-1 were increased in rat carotid arteries exposed to balloon injury (p < 0.01), and treatment with SPC could attenuate these effects (p < 0.05). Furthermore, balloon injury inhibited the protein expression of eNOS (p < 0.01), and SPC could elevate its level (p < 0.05). CONCLUSIONS: SPC could alleviate an intimal hyperplasia in balloon-injured carotid artery, and the mechanisms underlying this protective effect might be due to its inhibitory potency against inflammation signals. Our study also implies the potential applicability of SPC in treating restenosis after balloon angioplasty.

Sophocarpine prevents cigarette smoke-induced restenosis in rat carotid arteries after angioplasty.

BACKGROUND: Cigarette smoking is one of the main predisposing factors for atherosclerosis, which can lead to vascular inflammation. Emerging research has demonstrated that the rate of restenosis is increased following angioplasty in smokers. Sophocarpine, one of the Sophora alkaloids, can play the antiinflammatory role in cells. This study aimed to assess whether sophocarpine can alleviate the restenosis induced by cigarette smoke in rats post-angioplasty. METHODS: Fifteen male Sprague-Dawley rats were randomized into three groups (control group, smoking group, smoking and injected with sophocarpine group). An established balloon-induced carotid artery injury was performed to all the groups. For the balloon-injured carotid arteries, Verhoeff-Van Gieson stain was used to detect the area of neointima and media. Then the ratio of neointima to media (I/M ratio) was calculated. For the contralateral carotid arteries, the level of MAP kinase kinase 3 (MKK3), MAP kinase kinase 6 (MKK6), Phospho-MKK3/6, p38, Phospho-p38, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were measured. RESULTS: The I/M ratio of smoking group is larger than that of control group. However, sophocarpine could dramatically reduce the I/M ratio compared to smoking group. Cigarette smoke could induce the expression of Phospho-MKK3/6, Phospho-p38, IL-1ß and TNF-α, and treatment with sophocarpine could inhibit such effects. The levels of MKK3, MKK6 and p38 were not under the influence of cigarette smoke or sophocarpine. CONCLUSIONS: Sophocarpine could alleviate the cigarette smoke-induced restenosis in rat carotid arteries after balloon injury and the mechanism of its protective effect might be the inhibition of the inflammatory reaction. This also implies sophocarpine has the potential therapeutic applicability in preventing restenosis after angioplasty in smokers.

Role of perivascular adipose tissue in nicotine­induced endothelial cell inflammatory responses.

Smoking is considered to be one of the primary causes of atherosclerosis and vascular injury. Previous studies have shown that nicotine in tobacco can lead to vascular inflammation and endothelial dysfunction. Perivascular adipose tissue (PVAT) is known to secrete various types of adipokines to maintain vascular homeostasis. The present study investigated whether nicotine­induced PVAT malfunction can accelerate endothelial inflammation and eventually lead to endothelial dysfunction. The levels of inflammatory adipokines, including nuclear factor (NF)­κB, interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α, the ICAM­1 and VCAM­1 adhesion molecules and secretion of adiponectin were assessed in mature adipocytes and endothelial cells cultured alone or in co­culture under nicotine stimulation. It was found that nicotine reduced the secretion of adiponectin and stimulated secretion of the NF­κB, IL­1ß, IL­6 and TNF­α inflammatory adipokines in mature adipocytes. Although nicotine stimulated endothelial cells to secrete IL­1ß and IL­6, no significant increase in the secretion of TNF­α was observed. The co­culture of mature adipocytes with endothelial cells markedly augmented the expression of the NF­κB, IL­1ß, IL­6 and TNF­α inflammatory adipokines and the ICAM­1 and VCAM­1 adhesion molecules, and significantly lowered the levels of adiponectin. These findings suggested that nicotine induced mature adipocyte dysfunction, which caused the abnormal secretion of adiponectin and inflammatory adipokines, and exacerbated endothelial inflammation. These findings also suggested a mechanism whereby nicotine induced the secretion of adiponectin and inflammatory cytokines by adipocytes. The results of the present study elucidated a novel pathway induced by cigarette smoke, which contributed to atherosclerosis and vascular injury.

Heme oxygenase-1 alleviates cigarette smoke-induced restenosis after vascular angioplasty by attenuating inflammation in rat model.

Cigarette smoke is not only a profound independent risk factor of atherosclerosis, but also aggravates restenosis after vascular angioplasty. Heme oxygenase-1 (HO-1) is an endogenous antioxidant and cytoprotective enzyme. In this study, we investigated whether HO-1 upregulating by hemin, a potent HO-1 inducer, can protect against cigarette smoke-induced restenosis in rat's carotid arteries after balloon injury. Results showed that cigarette smoke exposure aggravated stenosis of the lumen, promoted infiltration of inflammatory cells, and induced expression of inflammatory cytokines and adhesion molecules after balloon-induced carotid artery injury. HO-1 upregulating by hemin treatment reduced these effects of cigarette smoke, whereas the beneficial effects were abolished in the presence of Zincprotoporphyrin IX, an HO-1 inhibitor. To conclude, hemin has potential therapeutic applications in the restenosis prevention after the smokers' vascular angioplasty.

Anti-oxidant effect of heme oxygenase-1 on cigarette smoke-induced vascular injury.

Cigarette smoking, a major independent risk factor of atherosclerosis, can cause oxidative and inflammatory damage of vascular tissue. Heme oxygenase-1 (HO-1) is an endogenous cytoprotective enzyme with an anti-oxidant role in cells. The aim of the present study was to investigate whether HO-1 was able to protect vascular and endothelial cells from the oxidative damage induced by cigarette smoking. It was observed that cigarette smoking was able to induce the generation of the reactive oxygen species (ROS) in carotid arteries of rats. Hemin, a widely used HO-1 inducer, was able to reduce the generation of ROS. In addition, when human umbilical vein endothelial cells (HUVECs) were cultured in the serum of smoking rats, this was able to increase ROS, and the protective effect of hemin was also observed in this system. In conclusion, the present study demonstrated that cigarette smoking causes oxidative damage of vascular cells and HUVECs by inducing the generation of ROS, while HO-1 has an anti-oxidant effect in this course. This also implied that hemin, an inducer of HO-1, may have potential therapeutic applicability in the prevention of vascular diseases caused by cigarette smoking.

[Research advances in endotension after endovascular abdominal aneurysm repair].

When more abdominal aortic aneurysms are repaired by endovascular approaches, the post-operative endotension without endoleak increase along with the extended follow-up. An early detection of such endotension and a proper differentiation from endoleaks are particularly important for the treatment decision-making. This article reviews the mechanism, diagnosis, and management of endotension.

The p-ERK-p-c-Jun-cyclinD1 pathway is involved in proliferation of smooth muscle cells after exposure to cigarette smoke extract.

An epidemiological survey has shown that smoking is closely related to atherosclerosis, in which excessive proliferation of vascular smooth muscle cells (SMCs) plays a key role. To investigate the mechanism underlying this unusual smoking-induced proliferation, cigarette smoke extract (CSE), prepared as smoke-bubbled phosphate-buffered saline (PBS), was used to induce effects mimicking those exerted by smoking on SMCs. As assessed by Cell Counting Kit-8 detection (an improved MTT assay), SMC viability increased significantly after exposure to CSE. Western blot analysis demonstrated that p-ERK, p-c-Jun, and cyclinD1 expression increased. When p-ERK was inhibited using U0126 (inhibitor of p-ERK), cell viability decreased and the expression of p-c-Jun and cyclinD1 was reduced accordingly, suggesting that p-ERK functions upstream of p-c-Jun and cyclinD1. When a c-Jun over-expression plasmid was transfected into SMCs, the level of cyclinD1 in these cells increased. Moreover, when c-Jun was knocked down by siRNA, cyclinD1 levels decreased. In conclusion, our findings indicate that the p-ERK-p-c-Jun-cyclinD1 pathway is involved in the excessive proliferation of SMCs exposed to CSE.

[Establishment and functional identification of a stable cell line overexpression heme oxygenase-1].

OBJECTIVE: To establish a stable cell line overexpression heme oxygenase-1 (HO-1) mediated by a modified lentivirus system and identify its function. METHODS: The HO-1 gene was amplified by polymerase chain reaction and cloned into the modified pLentiLox3.7 expression vectors. The recombinant plasmids were transfected into HEK293T cells and the HO-1 was detected by Western blot. The recombinant plasmids were transfected into HEK293T cells to produce the viruses, with the helping plasmids including plp1, plp2, and VSVG. HEK293T cells were infected by the viruses and the cells that can express HO-1 were identified by Western blot. The reactive oxygen species were detected in the HO-1-overexpression HEK293T cells and the normal cells after the adding of hydrogen peroxide. The same experiment was performed with human umbilical vein endothelial cells. RESULTS: The stable cell line that can overexpress HO-1 was established, which was verified by Western blot. The reactive oxygen species in the HO-1-overexpression HEK293T cells and human umbilical vein endothelial cells decreased obviously after exposure to hydrogen peroxide. CONCLUSIONS: The lentivirus-carrying HO-1 was successfully packaged and the stable cell line overexpression HO-1 was established. HO-1 can play a protective role in the course of oxidative damage.

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.

[Endovascular treatment of ruptured abdominal aortic aneurysm a clinical analysis of 13 cases].

OBJECTIVE: To evaluate the effect of endovascular aneurysm repair(EVAR) of ruptured abdominal aortic aneurysm(rAAA) and to summarize the experience. METHODS: The clinical data of 13 RAAA cases(males 11, females 2, age range 69-88) undergoing EVAR from February 2002 to February 2013 were retrospectively analyzed.It consisted of 10 atherosclerotic aneurysms and 3 pseudoaneurysms. CTA was finished in all of them. And they all undergone emergency surgery. RESULTS: All of the cases were successfully treated. During the perioperation , one suffered from contrast induced nephropathy and there were no deaths. During the follow-up, there were one case of type Ia endoleak treated by embolism and one case of rerupture pseudoaneurysm which abandoned treatment. CONCLUSION: Endovascular repair is the safe and effective treatment for ruptured abdominal aortic aneurysm.

Endovascular aneurysm repair in emergent ruptured abdominal aortic aneurysm with a 'real' hostile neck and severely tortuous iliac artery of an elderly patient.

BACKGROUND: Endovascular aneurysm repair (EVAR) has been a revolutionary development in the treatment of abdominal aortic aneurysms (AAAs). Meanwhile, unfavorable anatomy of the aneurysm has always been a challenge to vascular surgeons, and the application of EVAR in emergent and elderly patients are still in dispute. CASE PRESENTATION: A 79-year-old woman presented as an emergency of abdominal pain with acute hypotension, heart rate elevation and a rapid decrease of hemoglobin. Emergent computed tomographic angiography (CTA) showed a ruptured AAA (rAAA) extending from below the opening of bilateral renal arteries down to the celiac artery and elongated to both common iliac arteries. The hostile neck and severely tortuous iliac artery made the following procedure a great challenge. An emergent endovascular approach was performed in which an excluder aortic main body was deployed below the origin of the bilateral renal arteries covering the ruptured aortic segment. Two iliac legs were placed superior to the opening of the right hypogastric respectively. In order to avoid the type Ib endoleak, we tried to deploy another cuff above the bifurcation of the iliac artery. However, the severely tortuous right iliac artery made this procedure extremely difficult, and a balloon-assisted technique was used in order to keep the stiff wire stable. Another iliac leg was placed above the bifurcation of the left iliac artery. The following angiography showed a severe Ia endoleak in the proximal neck and therefore, a cuff was deployed distal to opening of the left renal artery with off-the-shelf solution. The patient had an uneventful recovery with a resolution of the rAAA. She is well and symptom-free 6 months later. CONCLUSION: Endovascular aneurysm repair (EVAR) in emergent elderly rAAA with hostile neck and severe tortuous iliac artery is extremely challenging, and endovascular management with integrated technique is feasible and may achieve a satisfactory early result.

Comparison of endovascular aortic repair and open surgical repair for ruptured abdominal aortic aneurysm.

OBJECTIVE: To compare the clinical efficacies of endovascular aortic repair(EVAR)and open surgical repair(OSR)for ruptured abdominal aortic aneurysm(rAAA). METHODS: The clinical data of 28 rAAA patients undergoing emergent treatment between February 2002 and February 2013 in PUMC Hospital were retrospectively reviewed. Among them 13 cases were treated by EVAR and 15 cases by OSR. RESULTS: Before the surgery,the general conditions,comorbidities,and hemodynamics were not significantly different between these two groups(all P>0.05),although the EVAR group had significantly higher mean age than OSR group(P=0.041). In the perioperative period,the EVAR group showed significantly lower 30-day mortality(P=0.044),less blood loss(P=0.005),less blood transfusion(P=0.003),less infusion quantity(P=0.000),shorter length of procedure(P=0.001),and shorter hospital stay(P=0.020). Also,the EVAR group had no severe perioperative complications and showed superior 1-year follow up survival(P<0.05). CONCLUSIONS: EVAR is an effective treatment for rAAA and can improve the clinical outcomes. EVAR may be adopted as the first-line treatment for rAAA,especially for the aged.

The protective effect of Bcl-xl overexpression against oxidative stress-induced vascular endothelial cell injury and the role of the Akt/eNOS pathway.

Restenosis after intraluminal or open vascular reconstruction remains an important clinical problem. Vascular endothelial cell (EC) injury induced by oxidative stress plays an important role in the development of intimal hyperplasia. In this study, we sought to evaluate the protective effects of Bcl-xl overexpression in vitro on oxidative stress-induced EC injury and the role of the Akt/endothelial nitric oxide synthase (eNOS) pathway. Human umbilical vein endothelial cells (HUVECs) exposed to hydrogen peroxide (H2O2, 0.5 mM) were used as the experimental oxidative stress model. The Bcl-xl gene was transferred into HUVECs through recombinant adenovirus vector pAdxsi-GFP-Bcl-xl before oxidative treatment. Cell apoptosis was evaluated by Annexin V/propidium iodide and Hoechst staining, caspase-7 and PARP cleavage. Cell viability was assessed using the cell counting kit-8 assay, proliferating cell nuclear antigen (PCNA) immunocytochemical detection and the scratching assay. Expressions of Akt, phospho-Akt and eNOS were detected by Western blotting. Our results showed that H2O2 induced apoptosis and decreased the cell viability of HUVECs. Bcl-xl overexpression significantly protected cells from H2O2-induced cell damage and apoptosis and maintained the cell function. Furthermore, the level of phospho-Akt and eNOS protein expression was significantly elevated when pretreated with Bcl-xl gene transferring. These findings suggest that Bcl-xl overexpression exerts an anti-apoptotic and protective effect on EC function. The Akt/eNOS signaling pathway is probably involved in these processes.

[Clinical trial on pancreatic duct stones caused by chronic pancreatitis].

OBJECTIVE: To determine the possible mechanism for chronic pancreatitis causing pancreatic duct stones. METHODS: A total of 172 patients with chronic pancreatitis (n=67), pancreatic duct stones (n=62), and pancreatic injury (n=43), admitted to from August 2000 to October 2008, preoperatively diagnosed by endoscopic retrograde cholangiopancreatograpby(ERCP) or computed tomography(CT), and intraoperatively confirmed by exploration and biopsy, were divided into 3 groups. Pancreatic fluid was drawn to test the concentrations of pancreatic stone protein (PSP), lactoferrin (LF) and Ca2+. RESULTS: The chronic pancreatitis (the CP group) presented hard consistency, shrinkage and nodular fibrosis of the pancreas; besides the above symptoms, the pancreatic duct stones (the PS group) presented dilatation of the pancreatic ductal system with various stones; pancreatic injury (the PI group) presented broken pancreas of different grades with fluid or blood. Compared with that of the PI group, PSP concentration of both the PS group and the CP group was elevated (P<0.05), and was more apparent in the CP group. Concentrations of LF and Ca2+ were also elevated (P<0.05), which were more obvious in the PS group. CONCLUSION: Decreased concentrations of PSP and increased concentrations of LF and Ca2+ may play very important roles in chronic pancreatitis causing pancreatic duct stones.