[Mechanism of n-butanol fraction of Wenxia Formula combining with gefitinib in treating non-small cell lung cancer based on network pharmacology and in vitro experiment].

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.

Intra-Sac Injection of Thrombin During Endovascular Aneurysm Repair to Remedy Type II Endoleak and Promote Sac Shrinkage.

PURPOSE: To evaluate the safety and effectiveness of intra-sac thrombin injection to remedy type II endoleaks (T2ELs) during endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: 224 cases abdominal aortic aneurysm (AAA) were treated with EVAR. For the 52 cases of intra-operative type II endoleaks and 8 cases of ruptured AAAs, after the grafts were deployed, thrombin was injected into the aneurysm sac through a preset catheter. The occurrence of endoleaks post-EVAR were followed up with by Computed Tomography (CT) angiogram. The diameter and the volume of the aneurysm sac were also measured. Endpoints included incidence of T2ELs, AAA sac shrinkage and re-intervention rate and all-cause mortality. RESULTS: The overall technical success rate was 100%. Fifty-two patients were followed up with for 9-56 (median 24) months. No serious complications were observed during follow-up. The incidence of endoleak was 5.8% (3/52) during follow-up. The maximum diameter of the aneurysm decreased from 61.1 ± 14.2 mm to 53.7 ± 10.6 mm, 47.9 ± 8.3 mm and 43.7 ± 7.2 mm (87.9%, 78.4% and 71.5% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively (P < .05). The volume of the aneurysm sac shrank from 236.2 ± 136.2 cm3 to 202.6 ± 114.1 cm3, 155.6 ± 68.4 cm3 and 129.7 ± 52.4 cm3 (85.8%, 65.9%, and 54.9% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively (P < .05). The rate of various endoleaks was 5.8% (3/52) and the re-intervention rate was 1.9% (1/52) in this research. CONCLUSIONS: Clinical outcomes show that intra-sac injection of thrombin during EVAR is safe and may be effective in remedying small amount and low-velocity endoleaks and promoting shrinkage of the aneurysm sac.

[Analysis on Clinical Characteristic and Risk Factors of Patients Coexistence of Cerebral Artery Stenosis with Unruptured Intracranial Aneurysm].

OBJECTIVE: To analyze the incidence of intracranial unruptured aneurysms in patients with intracranial artery stenosis,clinical features,and investigate the risk factors for unruptured intracranial aneurysms. METHODS: Medical records from all patients performed with digital subtraction angiography (DSA) who had been treated at Peking University Third Hospital,China,from January 2012 to December 2015 were retrospectively reviewed to identify cases coexistence with cerebral artery stenosis and unruptured intracranial aneurysm. RESULTS: Of 273 patients with cerebral artery stenosis (≥50%),intracranial unruptured aneurysms was observed in 17 cases (6.23%) from age of 45 to 78,among them 8 (47.06%) were female and 9 (52.94%) were male. The incidence of unruptured intracranial aneurysm in male patients was 4.17% (9/216),and that of female was 14.4% (8/57). There was statistically significant difference between the male and female incidence of intracranial aneurysm ( P<0.05). Of these 17 patients,16 (94.12%) aneurysms were located in the internal carotid artery (ICA) system,1 (5.88%) aneurysm was located at the tip of the basilar artery. In 11 cases (64.71%),aneurysms were located at the distal of the stenotic vessels,2 (11.76%) were located at the proximal of the stenotic vessels,and 4 cases (23.53%) of which the aneurysm and stenosis were not in the same artery. Logistic multivariate analysis showed that gender was an independent risk factor for aneurysms in patients with cerebral arterial stenosis. CONCLUSION: In the intracranial artery stenosis atients,the possibility of the occurrence of the aneurysm is much higher than the general population,and women were more prominent than man. Sex is an independent risk factor for aneurysms in patients with cerebral arterial stenosis.

[Endovascular treatment in cerebral artery tandem lesions].

OBJECTIVE: To evaluate the effectiveness and safety of endovascular treatment in solving symptomatic cerebral artery tandem lesions. METHODS: From June 2012 to February 2014, 12 cases (24 lesions) with symptomatic cerebral artery tandem lesions were accepted for the endovascular treatment. The distributions of the tandem lesions were as follows: the common carotid artery and internal carotid artery (1 case), the internal carotid artery and the proximal of the carotid cavernous sinus segment (3 cases), the internal carotid artery and the distal of the carotid cavernous sinus segment (4 cases), the intracranial segment of internal carotid artery and middle cerebral artery M1 segment (2 cases), the first segment of vertebral artery and intracranial segment of vertebral artery (2 cases). All of these cases were treated from distal lesions to proximal lesions except for tandem lesions in the internal carotid artery and the distal of the carotid cavernous sinus segment in order to obtain better support. Tandem lesions were treated in the same operation with local anesthesia or general anesthesia. The procedures of the 12 cases retrospectively were analyzed and the peri-operation complications and responsibility region recurrent ischemic stroke incidents observed. RESULTS: All tandem lesions were solved successfully all at once. There were no peri-operation complications or recurrent ischemic stroke incidents. There were no recurrent ischemic stroke incidents or stent restenosis cases in the follow-up. CONCLUSION: It is safe and effective for selective endovascular treatment in solving symptomatic cerebral artery tandem lesions at the same time, but we should take careful preoperative evaluation and improve the operation plan.

Isolated superior mesenteric artery dissection in China.

OBJECTIVE: This study investigated the status of isolated superior mesenteric artery (SMA) dissection in the most populous country, China. METHODS: The Chinese-language literature published before December 2014 was reviewed. All case reports and series were included. If multiple reports originated from the same hospital and included overlapping time frames, only the most recent report was included. The clinical characteristics, imaging features, and treatment were analyzed. "Symptom relief" was used as the outcome measure. RESULTS: A total of 622 patients (88.5% male) with isolated SMA dissection were found in the Chinese-language literature. Patients were a mean age of 55.4 years. Analysis of the demographic data showed that isolated SMA dissection was most reported from the developed areas of China. The most common symptom (91.1%) was abdominal pain, and 42.7% patients had hypertension as a complication. Contrast-enhanced computed tomography was used to diagnose 95.2% of patients. The mean distance from the SMA ostium to the beginning of the dissection was 20.1 mm (range, 0-65.0 mm). The mean length of dissection was 63.1 mm (range, 10.7-205.9 mm). The percentages of patients who underwent primary conservative, surgical, and endovascular treatments were 63.2%, 3.2% and 33.6%, respectively. As primary management, the symptom relief rate of conservative management, with or without anticoagulation, was 62.6% and 86.5%, respectively. The best result of conservative treatment was achieved in cases of Yun type I and Luan classification type B. The symptom relief rate of surgical and endovascular treatment was 100% and 95.2%, respectively. CONCLUSIONS: The incidence of isolated SMA dissection may not be as rare as previously reported. Endovascular treatment of isolated SMA dissection is commonly used in China as a first-line treatment.

[Relative factors of type II endoleak after endovascular aneurysm repair].

OBJECTIVE: To study the relative factors of type II endoleak after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms. METHODS: Twenty-eight cases of abdominal aortic aneurysms treated by EVAR were retrospectively analyzed. The characteristics of the inferior mesentery arteries (IMA), the arc Riolan and the lumbar arteries of the cases with or without type II endoleak were analyzed. RESULTS: Type II endoleak was found in 8 (28.6%) cases, of which, 2 were type IIa and 6 were type IIb. The diameter of the IMA originating part of the cases with type II endoleak [(4.03 ± 1.00) mm] was significantly bigger than that without endoleak [(2.89 ± 0.50) mm, P=0.007]. The number of the lumbar arteries originating from the aneurysm sac in cases with type II endoleak (3.4 ± 0.8) was significantly more than that without endoleak (1.9 ± 1.5, P=0.017). However, type II endoleak was irrelevant to the diameter of originating part of the lumbar arteries and the form of the arc Riolan. After the average 14.5 months follow-up, the aneurysm sac was found with shrinkage in 1 case, no change in 2 cases, and augment in 5 cases. Secondary transarterial embolization was performed for only 1 case. CONCLUSION: Type II endoleak was much easily found in cases with bigger diameter of originating part of the IMA, or in cases with more lumbar arteries originating from the aneurysm sac.

[Related factors of hemodynamic damage after carotid artery stenting].

OBJECTIVE: To analyze correlation factors of hemodynamic damage after carotid artery stenting. METHODS: In this study, 66 cases (71 lesions) who undertook carotid artery stenting were collected and the correlation factors of hemodynamic damage were analyzed. RESULTS: Hemodynamic damage emerged in 23 cases (32.4%), of which, 11.3% developed hypotension. The distance between bifurcation and lesions (P=0.0020), plaque distribution (P=0.0002), plaque character (P=0.0019), post-dilation (P=0.0026) were associated with hemodynamic damage by single factor analysis. However, only eccentric plaque (P=0.0153) and calcified plaque (P=0.0097) were associated with hemodynamic damage by multiple factors analysis. All the patients could reach stable circulation by drugs during operation, and no cerebral ischemic events (transient ischemic attack or stroke) and cardiovascular ischemic events happened. CONCLUSION: The distance between bifurcation and lesions, eccentric plaques, calcified plaques are correlation factors of hemodynamic damage.

[Morphological typing of the middle cerebral artery M1 segment by magnetic resonance angiography].

OBJECTIVE: To study the morphology of middle cerebral artery (MCA) M1 segment. METHODS: We selected the MRA data of 794 MCA (400 of the left side and 394 of the right side) from January 1, 2011 to June 30, 2011 consecutively and analyzed the morphology of the MCA M1 segment in axial, anteroposterior and lateral view, measured the length of the M1 segment, and analyzed the similarity of the left and right side M1 segment morphology. RESULTS: In axial, anteroposterior and lateral view, the MCA M1 segment showed C-shape > L-shape > S-shape. In axial view, it was about 373 (47%) M1 segment performance for the C-shape, of which 340 (42.8%) M1 segments showed bowing to the dorsal side, only 33 (4.2%) M1 segments showed bowing to the ventral side. In anteroposterior view, it was about 322 (40.6%) M1 segments of the performance of the C-shape, of which 262(33.0%) M1 segments showed a bowing to the superior, 60 (7.6%) showed bowing to the inferior. The similarity of the left and right MCA M1 segments was 27.2% (114/419) in axial view and 42.7% (179/419) in anteroposterior view. It was more similar in anteroposterior view than in axial view. Along with the increase of age, in the axial view, L-shape converted to C-shape very obviously, but only mildly elevated in S-shape. In anteroposterior view, the L-shape converted to the C-shape or S-shape along with the increase of age. CONCLUSION: The different morphology of MCA M1 segment in axial and anteroposterior view may be involved in the development of intracranial atherosclerosis.

[Clinical observation of middle cerebral artery angioplasty in treatment of subcortex cerebral watershed infarction with moderate or severe disabilities].

OBJECTIVE: To assess the safety and effectiveness of middle cerebral artery angioplasty in treatment of subcortical watershed infarcts (S-CWI) with moderate or severe disabilities. METHODS: From June 2011 to May 2012, 5 S-CWI patients (six lesions) with moderate or severe disabilities combining severe stenosis in Ipsilateral middle cerebral artery received middle cerebral artery angioplasty in Interventional Radiology and Vascular Surgery Department, Peking University Third Hospital. We observed the neurological score before and after angioplasty and assessed the improvement of neurological functions. RESULTS: The National Institute of Health stroke scale(NIHSS) scores were decreased by 4-6 points and modified Rankin scale(mRs) scores were decreased 1 point in 7 days. In the 3 months' follow-up, 4 patients' mRs scores were 1 point, and 1 patient's was 2 points. In the 1-year follow-up, there were no new strokes and instent restenosis events. CONCLUSION: Middle cerebral artery angioplasty in treatment of S-CWI with moderate or severe disabilities is beneficial.

[Efficacy of early consecutive lumbar puncture treatment in aneurysmal subarachnoid hemorrhage after embolization].

OBJECTIVE: To summarize the significance of lumbar punctures in remedy for aneurysmal subarachnoid hemorrhage (aSAH) after embolization. METHODS: From December 2002 to September 2011, 43 cases of aSAH underwent aneurysm embolization at department of interventional radiology and vascular surgery, Peking University Third Hospital. After the embolization,consecutive lumbar punctures were undertaken everyday, by which we measured proper cerebrospinal fluid pressure and slow drainage of cerebrospinal fluid. In accordance with the lumbar puncture results we determined the control of blood pressure, dehydration and rehydration therapy procedures. RESULTS: Two patients died. Only one patient in the 41 cases of the survived patients developed cerebral vasospasm, cerebral infarction and obstructive hydrocephalus, but by ventriculo-peritoneal shunt, obstructive hydrocephalus was relieved. The remaining 39 patients recovered well. After the mean follow-up of (26.0±5.8) months, no new neurological symptoms were found. CONCLUSION: Early consecutive lumbar puncture treatment in ASH after embolization is significant.

Vasodilator and endovascular therapy for isolated superior mesenteric artery dissection.

OBJECTIVE: We report our experience in the treatment of isolated superior mesenteric artery dissection and review the clinical and imaging features reported in the literature. METHODS: A retrospective study was conducted of 18 consecutive patients with isolated superior mesenteric artery dissection who presented at the Peking University Third Hospital between September 2008 and May 2012. Their clinical characteristics, including age, sex, medical history, risk factors, symptoms, diagnostic imaging modality, and treatment, were analyzed. Also reviewed were 278 patients with isolated superior mesenteric artery dissection reported in the English language literature. The epidemiology, mechanism, clinical presentation, imaging features, and treatment were discussed. RESULTS: There were 14 men and four women with a mean age of 55.6 years (range, 41-84 years). Four patients were asymptomatic, and 14 presented with acute-onset abdominal pain. The diagnosis was established by contrast-enhanced computed tomography in 17 patients and ultrasound imaging in one patient. All dissections were located at the anterior wall and around the convex curvature of the superior mesenteric artery. The decision to intervene was based on symptoms. Three asymptomatic patients underwent successful conservative management, and one asymptomatic patient with an aneurysmal dilated false lumen underwent endovascular stent placement. For the 14 symptomatic patients, definitive treatment included catheter-directed infusion of a vasodilator in four and stent placement combined with catheter-directed infusion of a vasodilator in 10, of whom one patient underwent hybrid stent placement. No complications or deaths occurred. During the mean 14.9-month (range, 1-40 month) follow-up period, all patients were asymptomatic, and patency of the superior mesenteric artery was demonstrated by contrast-enhanced computed tomography scan. CONCLUSIONS: Conservative management can be applied to asymptomatic patients with isolated superior mesenteric artery dissection. For symptomatic patients, stent placement is the definitive treatment if there is no arterial rupture or intestinal necrosis. Self-expanding bare stents that completely cover the curvature of the superior mesenteric artery are recommended. Catheter-directed infusion of a vasodilator can be an effective accessional process after stent placement.

[Histological character of intimal hyperplasia post jugular vein grafts and the protective effect of lovastatin].

OBJECTIVE: To investigate the characteristics of intimal hyperplasia and lovastatin's effects on canine jugular venous prosthesis bypass grafting. METHODS: In the study, 12 adult mistus dogs were randomly divided into 2 groups: lovastatin group and control group. All the dogs were performed with jugular venous prosthesis bypass grafting (ePTFE, 6 mm in diameter, and 5 cm in length). Four weeks later, all the 12 specimens were harvested. The patency and mural thrombus of grafts were evaluated. The characteristics of intimal hyperplasia were described and measured by HE staining and endothelial nitric oxide synthase (eNOs) immunohistochemical method. The differences between the two groups were compared. RESULTS: Four weeks later, 3 grafts with complete occlusion were found in the two groups separately. Apparent intimal hyperplasia was observed in all the grafts. The neointima of proximal and distal part in lovastatin group were thinner than in control group respectively (proximal P=0.045, distal P=0.040). The endothelial cells were found in the surface of neointima. Newly born vessels could be found in the neointima and the new vessels were more in lovastatin group than in control group (proximal P=0.041, distal P=0.031). CONCLUSION: At the end of 4 weeks, the intimal hyperplasia with neovascularization was obviously near the anastomosis. Lovastatin showed the ability to inhibit the intimal hyperplasia and promote the neovascularization.

[Experience in treatment of Raynaud's syndrome by chemical sympathectomy: 97 cases].

OBJECTIVE: To summarize the curative effect in treatment of Raynaud's syndrome with chemical thoracic sympathectomy (CTS) guided by X-ray since 2001. METHODS: From March 2001 to August 2007, 97 patients with Raynaud's syndrome (186 limbs) were treated by CTS. Guided by X-ray, a needle was punctured through the back skin to the second thoracic sympathetic ganglion beside the thoracic vertebrae and 2 mL of 5% (v/v) phenol was injected. RESULTS: The first CTS treatment produced a good effect on 146 limbs with an effective rate of 78.5% (146/186). The same treatment was performed on the limbs with no effect 1-2 days after the first treatment and produced good effect on 13 limbs with an effective rate of 32.5% (13/40). The total effective rate of the patients who were hospitalized for the first time was 85.5% (159/186). Of the 97 patients, 78 patients (80.4%) were followed up for 47 months on an average with an effective rate of 69.5%. And the rate of complications was 11.4% for pheumothorax, and 3.9% for hydrothorax. Hyperalgesia on axillary region and anterior chest wall; Horner syndrome and sinus bradycardia were rare. CONCLUSION: CTS is minimally invasive and effective in treatment of Raynaud's syndrome.

[A case of multiple tuberculous aneurysm of the abdominal aorta].

Tuberculous aneurysm of the aorta is a very rare disorder. There have been only 50 reported cases of tuberculous aneurysm since 1895 till now, of which 88% were false aneurysms with majority being single in number. And only four were found to have multiple tuberculous aneurysms. The mean ages of the patients were 50+/-16 years. Treatment of tuberculous aortic aneurysm must be a combined medical and surgical approach. Once tuberculous aneurysm is identified, surgery must be performed promptly. The size of the aneurysm does not influence the need for surgery. A 70-year-old male with intermittent episodes of abdominal pain after receiving an inappropriate antitubercular therapy for pulmonary tuberculosis was diagnosed as multiple false tubercular aneurysm of abdominal aorta. An aneurysm of base 3.3 cm and greatest diameter 5 cm x 6 cm was seen just above the opening of Coeliac trunk. Also at the dorsal aspect of abdominal aorta and superior mesenteric artery junction and ventral aspect of renal artery false aneurysms were seen, each with the size of 1 cm in diameter. Apart from antitubercular and antimicrobial treatment, first line surgery Endovascular Exclusion of Abdominal Aortic Aneurysm was performed for ruptured false abdominal aortic aneurysm. Even before the second line surgery, smaller abdominal aortic aneurysms got ruptured and the patient's party gave up further treatment. Finally the patient died of gastrointestinal haemorrhage.