In the background of the high incidence and high mortality of cardiovascular diseases,atherosclerosis is the main pathological feature of cardiovascular diseases and the core pathological basis for disease progression. In the evolution of atherosclerotic plaques,the rupture of unstable plaques,plaque shedding and formation of thrombosis are the most dangerous parts. In this process,the formation of plaque fibrosis is the core mechanism regulating plaque stability. Additionally,fibrosis reflects dynamic changes in the inflammatory processes and pathological changes. In view of the inflammation regulation and fibrosis regulation,this paper clarified the process of atherosclerotic plaque,explained the roles of relevant inflammatory cells and cytokines in plaque stability,and summed up drug researches related with stable plaque in recent years. In the future,improving the fibrosis will be a new idea for stabilizing plaque in atherosclerosis drug development.
Atherosclerosis ; drug therapy ; pathology ; Cytokines ; Fibrosis ; Humans ; Inflammation ; Plaque, Atherosclerotic ; drug therapy ; pathology ; Thrombosis ; drug therapy ; pathology

Objective To explore the effect of qi-regulating,phlegm-resolving,and blood-promoting prescription on coronary microvascular thrombosis and coronary microvascular occlusion in rat models. Methods Totally 125 healthy clean-grade male SD rats weighing (300±25) g were sequentially numbered and then randomly divided into treatment group (n=60),control group (n=60) and blank group (n=5).Rats in the treatment group and control group received apical left ventricular injection of sodium laurate to establish rat models of coronary microvascular thrombosis. Then,rats in the control group were given distilled water by gavage one day before operation and after surgery. In contrast,rats in the treatment group were given qi-regulating,phlegm-resolving,and blood-promoting prescription by gavage one day before operation and after surgery. Five rats from both treatment group and control group were killed at each of six time points (1 hour,24th hour,7th day,14th day,21th day,and 28th day),and the myocardium specimens were harvested. The 5 rats in the blank group did not receive any special treatment and were given normal feeding;in the 28th day,they were sacrificed to obtain the myocardial specimens. Pathological sections of rat myocardial tissues were made to observe and compare the degrees of coronary microvascular thrombosis and coronary microvascular obstruction.Results In the treatment group and the control group,coronary microvascular thrombosis occurred 1 hour after apical sodium laurate injection and reached the peak at the 24th hour. Compared with the blank group,the treatment group and the control group showed different degree of coronary microvascular obstruction. Comparison between the treatment group and the control group at each time point showed that the coronary microvascular thrombosis in the treatment group was significantly lower than that in the control group (P<0.05 or P<0.01).The severity of coronary microvascular occlusion was significantly milder in the treatment group than in the control group (P<0.05 or P<0.01).Conclusions Apical left ventricular injection of sodium laurate successfully established rat models of coronary microvascular thrombosis. Qi-regulating,phlegm-resolving,and blood-promoting prescription can reduce coronary microvascular thrombosis and improve coronary microvascular obstruction.
Animals ; Coronary Occlusion ; drug therapy ; Coronary Thrombosis ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Male ; Myocardium ; pathology ; Qi ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To explore the expression of CyPA and CD147 in rabbit models of vulnerable carotid atherosclerotic plaque and the therapeutic effect of atorvastatin.
 METHODS: Twenty-four male New Zealand rabbits were randomly divided into 3 groups. Eight rabbits were served as a normal diet group (Group A), and the remaining 16 rabbits underwent balloon-induced endothelial injury in the right carotid artery and thereafter were fed on high-cholesterol diet (1% cholesterol) for 12 weeks, then they were divided into 2 groups: a AS group (Group B), an atorvastatin group [Group C, 2.5 mg/(kg.d)]. 4 weeks later, plaque disrupture was triggered by China Russell's viper venom and histamine. Serum levels of TC, TG, LDL-C and HDL-C were measured at different timepoint. The damaged carotid arteries were collected to undergo pathological examination. The macrophage, expression of CyPA and CD147 were detected by immuno-histochemical analysis, and the mRNA levels of CyPA and CD147 were examined by reverse transcription polymerase chain reaction (RT-PCR).
 RESULTS: Compared with the Group A, the serum levels of TC and LDL-c in the Group B and Group C were significantly increased (all P<0.01). Compared with the Group B, the serum levels of TC and LDL-c in the Group C were reduced significantly after atorvastatin intervention for 4 weeks (all P<0.01). The plaques disruption and thrombosis occurred in 4 out of the 6 rabbits in the Group B, while only 1 rabbit demonstrated plaques disruption and thrombosis in the Group C. Compared with the Group B, the levels of CyPA, CD147 and macrophage in carotid atherosclerotic plaque in the Group C were decreased significantly (all P<0.01).
 CONCLUSION The up-regulation of CyPA and CD147 may be involved in pathogenesis of vulnerable carotid atherosclerotic plaque. Atorvastatin could stabilize the plaque through inhibiting the CyPA and CD147 expression.
Animals ; Atorvastatin ; pharmacology ; Basigin ; metabolism ; Carotid Artery, Common ; pathology ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; Cyclophilin A ; metabolism ; Macrophages ; cytology ; Male ; Plaque, Atherosclerotic ; drug therapy ; metabolism ; Rabbits ; Random Allocation ; Thrombosis ; pathology ; Triglycerides ; blood

Portal vein thrombosis is an uncommon but an important cause of portal hypertension. The most common etiological factors of portal vein thrombosis are liver cirrhosis and malignancy. Albeit rare, portal vein thrombosis can also occur in the presence of local infection and inflammation such as pancreatitis or cholecystitis. A 52-year-old male was admitted because of general weakness and poor oral intake. He had an operation for colon cancer 18 months ago. However, colonic stent had to be inserted afterwards because stricture developed at anastomosis site. Computed tomography taken at admission revealed portal vein thrombosis and inflammation at colonic stent insertion site. Blood culture was positive for Escherichia coli. After antibiotic therapy, portal vein thrombosis resolved. Herein, we report a case of portal vein thrombosis with sepsis caused by inflammation at colonic stent insertion site which was successfully treated with antibiotics.
Anti-Bacterial Agents/therapeutic use ; Cholecystitis/etiology ; Colonic Neoplasms/pathology/therapy ; Escherichia coli/isolation & purification ; Escherichia coli Infections/drug therapy/etiology ; Humans ; Inflammation/*etiology ; Liver/diagnostic imaging ; Male ; Middle Aged ; Pancreatitis/etiology ; Portal Vein ; Sepsis/*diagnosis/drug therapy/microbiology ; Sigmoidoscopy ; Stents/*adverse effects ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/*diagnosis

Aged ; Endovascular Procedures ; Fibrinolytic Agents ; therapeutic use ; Humans ; Lower Extremity ; pathology ; surgery ; Male ; Stents ; Thrombolytic Therapy ; methods ; Thrombosis ; drug therapy ; surgery

OBJECTIVETo evaluate the thrombus length on CT perfusion imaging and to assess its predictive value for recanalization and clinical outcome after intravenous thrombolysis therapy (IVT).

METHODSFifty-six consecutive acute ischemic stroke patients with proximal middle cerebral artery (M1 segment) occlusion underwent CT perfusion imaging examination before IVT between June 2009 and May 2015. The onset-to needle time was (214.3 ± 82.0) min, and the pretreatment NIHSS score of patients was 13 (IQR 8-17). The thrombus length was determined as the distance between the proximal and distal thrombus end delineated on dynamic angiography, which was reconstructed from CT perfusion source images. Recanalization was evaluated according to Arterial Occlusive Lesion (AOL) scale, and functional outcome was based on modified Rankin scale (mRS) 3 months after IVT. Logistic regression model was used to investigate the relationship between thrombus length and recanalization, and the optimal cut-off points were determined by receiver operating characteristic curve (ROC).

RESULTSAmong 56 patients, 42 (75%) achieved recanalization 24 h after IVT with mean thrombus length of (9.0 ± 4.7) mm; and 14 (25%) patients remained occlusion with mean thrombus length of (10.0 ± 5.4) mm. Logistic regression analysis demonstrated that thrombus length was an independent predictor for both recanalization (OR=0.869; 95% CI:0.764-0.987; P=0.031) and unfavorable outcome (OR=1.180;95% CI:1.023-1.362; P=0.023). Thrombus length of 11.3 mm was identified as the optimal cut-off value for recanalization (AUC=0.697, sensitivity 71.4%, specificity 76.2%), while thrombus length of 9.9 mm was the optimal cut-off value for unfavorable functional outcome (AUC=0.689, sensitivity 64.7%, specificity 71.4%).

CONCLUSIONThe thrombus length evaluated on CT perfusion imaging is an effective predictor for recanalization and unfavorable outcome after IVT in acute ischemic stroke patients with middle cerebral artery occlusion.

Angiography ; Humans ; Infarction, Middle Cerebral Artery ; pathology ; Logistic Models ; Perfusion Imaging ; Sensitivity and Specificity ; Stroke ; diagnosis ; drug therapy ; Thrombolytic Therapy ; Thrombosis ; diagnosis ; drug therapy ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Portal-vein thrombosis (PVT) develops in 10-25% of cirrhotic patients and may aggravate portal hypertension. There are few data regarding the effects of anticoagulation on nonmalignant PVT in liver cirrhosis. The aim of this study was to elucidate the safety, efficacy, and predictors of response to anticoagulation therapy in cirrhotic patients. METHODS: Patients with liver cirrhosis and nonmalignant PVT were identified by a hospital electronic medical record system (called BESTCARE). Patients with malignant PVT, Budd-Chiari syndrome, underlying primary hematologic disorders, or preexisting extrahepatic thrombosis were excluded from the analysis. Patients were divided into two groups (treatment and nontreatment), and propensity score matching analysis was performed to identify control patients. The sizes of the thrombus and spleen were evaluated using multidetector computed tomography. RESULTS: Twenty-eight patients were enrolled in this study between 2003 and 2014: 14 patients who received warfarin for nonmalignant PVT and 14 patients who received no anticoagulation. After 112 days of treatment, 11 patients exhibited significantly higher response rates (complete in 6 and partial in 5) compared to the control patients, with decreases in thrombus size of >30%. Compared to nonresponders, the 11 responders were older, and had a thinner spleen and fewer episodes of previous endoscopic variceal ligations, whereas pretreatment liver function and changes in prothrombin time after anticoagulation did not differ significantly between the two groups. Two patients died after warfarin therapy, but the causes of death were not related to anticoagulation. CONCLUSIONS: Warfarin can be safely administered to cirrhotic patients with nonmalignant PVT. The presence of preexisting portal hypertension is a predictor of nonresponse to anticoagulation.
Aged ; Anticoagulants/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/complications/*diagnosis ; Male ; Middle Aged ; Portal Vein ; Propensity Score ; Severity of Illness Index ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/*drug therapy/pathology ; Warfarin/therapeutic use

OBJECTIVETo investigate the effects of Qushuanling Capsule ( QSLC) on thrombus formation and platelet aggregation in rats.

METHODSArteriovenous bypass, venous thrombosis, and middle cerebral artery thrombosis models were used in rats to investigate the anti-thrombotic effects of QSLC, a compound of nine Chinese herbs. The platelet aggregation induced by adenosine diphosphate (ADP), thrombin or arachidonic acid (AA), as well as the contents of thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1α (6-keto-PGF1α) in rat plasma and aortic walls, were determined to investigate the possible mechanisms of the anti-thrombotic effects of QSLC.

RESULTSAfter oral administration with QSLC for 7 days, arteriovenous bypass thrombosis was obviously suppressed compared with the model group, venous thrombosis was also obviously suppressed, rat behaviors were obviously improved, and brain infarct size as well as water content were also reduced. The platelet aggregation induced by ADP or thrombin was inhibited by QSLC, but the drug had no effect on AA-induced platelet aggregation and content of TXB(2) and 6-keto-PGF1α in plasma and the aortic wall.

CONCLUSIONThese results suggest that QSLC can be used in the prevention and treatment of thrombotic diseases, and that its mechanism of action may be related to inhibition of platelet aggregation.

6-Ketoprostaglandin F1 alpha ; blood ; Adenosine Diphosphate ; pharmacology ; Animals ; Aorta ; drug effects ; metabolism ; pathology ; Cerebral Infarction ; blood ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Middle Cerebral Artery ; drug effects ; pathology ; Platelet Aggregation ; drug effects ; Rats ; Rats, Sprague-Dawley ; Thrombosis ; drug therapy ; pathology ; Thromboxane B2 ; blood ; Venous Thrombosis ; drug therapy ; pathology

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
Adult ; Aged ; Aged, 80 and over ; Anorexia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/pathology ; Diarrhea/chemically induced ; Disease-Free Survival ; Fatigue/chemically induced ; Female ; Hand-Foot Syndrome/etiology ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/*drug therapy/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nausea/chemically induced ; Neoplasm Invasiveness ; Niacinamide/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/adverse effects/*therapeutic use ; Portal Vein/*pathology ; Proportional Hazards Models ; Tomography, Spiral Computed ; Venous Thrombosis/*drug therapy/pathology

OBJECTIVETo observe the regulatory effect of Chinese drugs for activating blood circulation (ABC) and for activating blood circulation and detoxifying (ABCD) on indices of thrombosis, inflammatory reaction, and tissue damage in a rabbit model of toxin-heat and blood stasis syndrome.

METHODSFifty-four rabbits were randomized into the normal control group, model group, simvastatin group (simvastatin, 0.93 mg/kg per day), ABC group [Xiongshao Capsule, 0.07 g/kg per day], and ABCD group [Xiongshao Capsule, 0.07 g/kg per day, and Huanglian Capsule, 0.14 g/kg per day]. All except the normal control group received a single injection of bovine serum albumin and were fed with high-fat diets for 6 weeks. At the end of week 4 of giving high-fat diets, a dose of endoxitin was given by ear vein injection, and a randomized 2-week treatment was initiated. At the end of treatment, blood lipids, circulating endothelial cells, and the pathological changes of the aortic arch were assessed. The serum levels of matrix metalloproteinases (MMP-9), tissue inhibitors to metalloproteinase (TIMP-1), granule membrane protein-140 (GMP-140), plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α) were determined.

RESULTSCompared with the model group, ABCD group showed decreased serum triglyceride (TG) level, improvement in the pathological change in the aortic arch, and reduction in the number of circulating endothelial cells (4.00 ± 1.41 per 0.9 μL for ABCD group vs 7.83 ± 1.72 per 0.9 μL for the model group). In addition, the levels of serum GMP-140, PAI-1, and IL-6 in ABCD group were also significantly reduced [0.79 ± 0.20 ng/mL, 5.23 ± 1.39 ng/mL, 40.64 ± 10.11 pg/mL for ABCD group vs 1.08 ± 0.31 ng/mL, 7.28 ± 2.01 ng/mL, 54.44 ± 13.56 pg/mL for the model group, respectively, P < 0.05]. A trend showing improvement in the indices of thrombosis, inflammatory reaction, and tissue damage was observed in the ABC group when compared to the model group, but the changes were not statistically significant (P > 0.05).

CONCLUSIONSChinese drugs for activating blood circulation and detoxifying have beneficial effects on regulating indices of thrombosis (GMP-140 and PAI-1) and inflammatory reaction (IL-6) in rabbit model with toxic-heat and blood stasis. The effect of the activating blood circulation and detoxifying drugs in regulating the levels of serum GMP-140, PAI-1, and IL-6 was superior to that of the activating blood circulation drugs.

Analysis of Variance ; Animals ; Atherosclerosis ; drug therapy ; pathology ; Blood Circulation ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Endothelium, Vascular ; drug effects ; pathology ; Immunohistochemistry ; Inflammation ; drug therapy ; pathology ; Male ; Rabbits ; Random Allocation ; Sensitivity and Specificity ; Simvastatin ; administration & dosage ; Systemic Inflammatory Response Syndrome ; drug therapy ; pathology ; Thrombosis ; drug therapy ; pathology