Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3ß signaling pathway.

BACKGROUND: Diabetic encephalopathy is manifested by cognitive dysfunction. Salidroside, a nature compound isolated from Rhodiola rosea L, has the effects of anti-inflammatory and antioxidant, hypoglycemic and lipid-lowering, improving insulin resistance, inhibiting cell apoptosis, and protecting neurons. However, the mechanism by which salidroside alleviates neuronal degeneration and improves learning and memory impairment in diabetic mice remains unclear. OBJECTIVE: To investigate the effects and mechanisms of salidroside on hippocampal neurons in streptozotocin-induced diabetic mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into 4 groups to receive either sham (control group (CON)), diabetes mellitus (diabetes group (DM)), diabetes mellitus + salidroside (salidroside group (DM + SAL)), and diabetes mellitus + salidroside + phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (diabetes mellitus + salidroside + LY294002 group (DM + SAL + LY294002)). After 12 weeks of diabetes onset, the cognitive behaviors were tested using Morris water maze. The number of hippocampal neurons was detected by Nissl staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, GSK-3ß, p-GSK-3ß, cleaved caspase-3, caspase-3, Bax, Bcl-2, MAP2, and SYN in the hippocampus were detected by Western blot. Moreover, the expression of MAP2 and SYN in the hippocampus was further confirmed by immunofluorescence staining. RESULTS: Salidroside increased the time of diabetic mice in the platform quadrant and reduced the escape latency of diabetic mice. Salidroside also increased the expression of p-PI3K, p-Akt, p-GSK-3ß, MAP2, SYN, Bcl-2, while suppressed the expression of cleaved caspase-3, caspase3, and Bax in the DM + SAL group compared with the DM group (P < 0.05). The Nissl staining showed that the number of hippocampus neurons in the DM + SAL group was increased with the intact, compact, and regular arrangement, compared with the DM groups (P < 0.05). Interestingly, the protective effects of salidroside on diabetic cognitive dysfunction, hippocampal morphological alterations, and protein expressions were abolished by inhibition of PI3K with LY294002. CONCLUSIONS: Salidroside exerts neuroprotective properties in diabetic cognitive dysfunction partly via activating the PI3K/Akt/GSK-3ß signaling pathway.

Protective effects and regulatory mechanisms of melatonin in a neonatal mouse model of LPS-induced inflammation.

This experiment mainly explored the protective effect and regulatory mechanism of melatonin (MEL) through its receptor on central nervous system (CNS) inflammation induced by lipopolysaccharide (LPS). The experiment was first divided into the following four groups: control group (CTRL group), LPS-induced inflammation model group (LPS group), LPS-treated MEL group (LPS + MEL group), and MEL administration group (MEL group). Later, a luzindole-antagonized LPS-MEL cotreatment group (LPS + MEL + LUZ group) was added to clarify the experimental results. ELISA was used to determine the inflammatory factor levels IL-6, IL-1ß, and IL-10 in brain slices. Western blotting was used to determine the expression levels of the microglia-specific protein CD11b and melatonin receptors MT1 and MT2 in brain slices. A large amount of IL-6 release and increased expression of CD11b protein were detected 24 h after inflammatory stimulation, while pretreatment with MEL inhibited the release of IL-6 and increased the expression of CD11b. At the same time, LPS induction downregulated the relative protein expression levels of MT1 and MT2. In addition, compared with the CTRL group and the LPS + MEL group, the administration of LUZ inhibited the protein expression of MT1. It increased the release of IL-1ß and IL-10, further indicating that MEL can alleviate LPS-induced neuroinflammation through the MT1 response. In short, MEL can reduce the neuroinflammatory response induced by LPS and exhibit related protective effects through MT1.

Anemia in patients with Takayasu arteritis: prevalence, clinical features, and treatment.

BACKGROUND: Anemia is a common comorbidity of patients with Takayasu arteritis (TA). This study evaluated the prevalence, clinical characteristics, and treatment in Chinese TA patients with anemia. METHODS: This retrospective study included 533 consecutive patients hospitalized for TA from January 2009 to April 2018. Anemia was diagnosed on the basis of hemoglobin level, according to World Health Organization criteria. RESULTS: A total of 194 patients (36.4%) were diagnosed with anemia. Most had mild anemia (177, 91.2%). Female patients were predominant (92.8% of anemic patients). Normocytic anemia (62.9%) was the most common pattern. Anemic patients were more likely than non-anemic patients to have dizziness (29.4% vs. 21.2%), low body mass index (22.0 ± 3.6 vs. 22.9 ± 3.4 kg/m2), and active disease stage (64.9% vs. 50.1%); pulmonary involvement (12.4% vs. 26.8%), pulmonary hypertension (12.9% vs. 20.1%) and pulmonary hypertensive-target drugs (2.8% vs. 11.6%) were less common among anemic than non-anemic patients (all P < 0.05). Larger left ventricular end-diastolic diameter and lower left ventricular ejection fraction were observed in anemic patients. Over a median follow-up of four months, the increase of hemoglobin in anemic patients was associated with the use of iron supplementation. CONCLUSIONS: Anemia is a very common concurrent condition in TA, especially in young, female patients. Patients with anemia are more likely to be in the active disease stage. Iron supplementation helps increase hemoglobin.

Association of interleukin-6 and interleukin-10 expression, gene polymorphisms, and Takayasu arteritis in a Chinese Han population.

Takayasu arteritis (TA) is a chronic inflammatory disease. Interleukin (IL)-6 and IL-10 are important cytokines involved in the immune response of TA in some ethnicities. We investigated whether the single-nucleotide polymorphism (SNP) of IL-6 and IL-10 genes and their expressions were associated with TA in a Chinese Han population. One hundred eighty-four TA patients and 235 healthy controls (HC) were recruited. DNA and RNA were extracted from peripheral blood cells. Genotyping of IL-6 and -10 was performed using polymerase chain reaction-ligase detection reaction (PCR-LDR). The mRNA levels of IL-6 and IL-10 were semi-quantified using reverse transcription polymerase chain reaction (RT-PCR) and real-time polymerase chain reaction (real-time PCR). Plasma levels of them were examined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-6 in active phase of TA were higher than those in stable phase (p = 0.015); the IL-10 in active phase was lower compared with stable phase (p = 0.046). Plasma levels of IL-6 in TA were higher than those in HC (p = 0.024). Plasma levels of IL-10 showed no difference between the two groups (p = 0.264). Plasma levels of IL-6 in active phase were increased than those in stable phase (p = 0.043) while those of IL-10 were decreased in active phase (p = 0.041). We found no significant differences between TA and HC in the frequency of any of the variations in the SNPs of IL-6 and IL-10 genes. The expression levels of both cytokines were associated with the disease status, indicating that they may serve as potential biomarkers for monitoring disease activity.

Cardiac Valve Involvement in Takayasu Arteritis Is Common: A Retrospective Study of 1,069 Patients Over 25 Years.

BACKGROUND: Takayasu arteritis (TA) can involve the aortic root or cardiac valves, resulting in hemodynamic disorders. In this study, we focused on the prevalence and clinical characteristics of TA patients with valve regurgitation. MATERIALS AND METHODS: We retrospectively assessed the clinical data in the electronic medical records of 1,069 consecutive patients with TA admitted to Fuwai Hospital from January 1992 to August 2017. We evaluated the valvular structure and function mainly by cardiac ultrasound. RESULTS: Among the 1,069 patients, 373 (34.9%) had valve regurgitation. The female to male ratio was 4.8:1. The average age at symptom onset was 28.1 ± 10.6 years. The median duration from symptom onset to first hospitalization was 65.9 months. Of patients with valve involvement, 47.4% and 40.1% had a high erythrocyte sediment rate and C-reactive protein level, respectively, at the time of echocardiography. Most patients (69.7%) had aortic regurgitation, and nearly half had moderate to severe aortic regurgitation. A total of 38.8% of patients had aortic valve damage, and 23.3% had involvement of the ascending aorta. Most other valve insufficiency was mild, including mitral regurgitation in 39.1% of patients, tricuspid regurgitation in 34.6%, and pulmonary regurgitation in 11.8%. Valve stenosis was rare. Misdiagnosis of other cardiac diseases occurred in 13 patients. CONCLUSIONS: Cardiac valve insufficiency is common in Chinese TA patients. Patients should undergo echocardiography once TA is diagnosed. In young women of reproductive age, TA should be considered when aortic regurgitation is detected.

The presentation and management of hypertension in a large cohort of Takayasu arteritis.

The objective of this study was to explore the presentation and management of hypertension secondary to Takayasu arteritis (TA) in a large cohort, single center in China. We retrospectively analyzed 381 TA patients with hypertension hospitalized in Fuwai hospital between Jan. 2004 and Feb. 2014. Diagnosis of hypertension was according to clinic blood pressure or the central blood pressure measured during angiography. Renal artery stenosis was the most common cause (264, 69.3%), followed by the thoracic descending aorta stenosis (98, 25.7%), abdominal aorta stenosis (78, 20.5%), and severe aortic regurgitation (45, 11.8%). More than two kinds of pathologies were found in 98 (25.7%) patients. The mean age of hypertension onset was 25.0 ± 14.3 years. The mean blood pressure of upper extremity in patients without bilateral subclavian artery stenosis (321, 84.3%) was 176.0 ± 29.4 mmHg/97.2 ± 23.0 mmHg, while in 60 (15.7%) patients with bilateral subclavian artery stenosis, the mean central blood pressure was 192.7 ± 30.8 mmHg/102.4 ± 121.1 mmHg. A total of 305 were followed for 38.4 ± 36.7 months, and the rate of blood pressure control, improvement, and failure was 50.8, 41.0, and 8.2%, respectively. Immunosuppressive therapy (OR 2.402, 95% confidence interval 1.253-4.603, P = 0.008) and the pathogenesis of hypertension (P = 0.010) were associated with prognosis of hypertension. The pathogenesis of hypertension due to TA is very complex and multifactorial. Renal artery stenosis is most frequently observed, followed by stenosis of the thoracic descending aorta, abdominal aorta, and severe aortic regurgitation. Immunosuppressive therapy and identifying the pathogenesis of hypertension is of great importance in patients with TA.

Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson's Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway.

BACKGROUND/AIMS: Parkinson's disease (PD) is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB), an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. METHODS: PD was introduced in rats via injection of lipopolysaccharide (LPS) into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), CD11b and ionized calcium binding adaptor molecule (IBA)-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. RESULTS: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. CONCLUSION: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

Aortic Aneurysm in Takayasu Arteritis.

BACKGROUND: Aortic aneurysm (AA) is a severe complication of Takayasu arteritis (TA). This study aimed to evaluate the prevalence, clinical and imaging features, management and long-term outcomes of AA in patients with TA. MATERIALS AND METHODS: A retrospective study was performed of TA patients with AA admitted to Fuwai Hospital from 1996-2015. Baseline clinical data and follow-up data of TA patients with AA were collected and analyzed. RESULTS: Thirty-nine (4.2%) of 934 patients with TA were identified with AA that was related to vasculitis. The mean age at disease onset was 31 ± 10 years, with a female-to-male ratio of 1.79:1. The ascending aorta was the most common site of the aneurysmal lesion (18, 33.3%), and the most frequent manifestations associated with AA were chest tightness (12, 30.8%) and shortness of breath (12, 30.8%), which were usually concomitant with aortic valve insufficiency. Involvement of multiple sites in AA was found in 8 patients (20.5%), and multiple AAs were found in 5 patients (12.8%). No significant difference was observed in clinical and imaging findings between sexes. Of 25 patients (64.1%) with a median 72-month follow-up, 1 patient suffered from heart failure owing to perivalvular leakage, and 1 patient died, possibly related to severe complications of the operation. CONCLUSIONS: The prevalence of AA is relatively low in Chinese patients with TA. AA seems to develop more frequently in male patients with TA. Management should consider location and size of AA, complexity of vessel lesions and disease status. Long-term follow-up is indispensable.

Aortic Dissection in Takayasu Arteritis.

BACKGROUND: Aortic dissection (AD) is a rare complication of Takayasu arteritis (TA). The clinical presentation and long-term management outcomes of AD in patients with TA have not been well described. MATERIALS AND METHODS: We conducted a retrospective study of patients with TA along with AD admitted to Fuwai Hospital between January 1985 and March 2016. Clinical data and follow-up data were collected and analyzed. RESULTS: Of the 1,154 patients with TA, we identified 10 patients (0.87%) with AD, which was likely to be associated with vasculitis. All patients were females with a median age at TA onset of 26.5 years (range: 18.3-33.3 years), had type III TA and had a history of hypertension, which was much more common than that in previously reported cases. Stanford type B or DeBakey category III was the dominant anatomic classification of AD. Four patients developed AD after the diagnosis of TA, and 6 developed AD near the time of TA diagnosis. Nine patients underwent conservative treatment, whereas 1 patient underwent endovascular repair due to extensive dissection. At a median 70.5-month follow-up (range: 31.5-138.5), we found that 7 patients had no AD progression, 1 patient had progressed without symptoms, 1 patient was lost and 1 patient died. CONCLUSIONS: Patients with TA along with long-standing and poorly controlled hypertension are liable to develop AD. Those with extensive AD in TA should be carefully treated and intensively followed up.

Melatonin represses oral squamous cell carcinoma metastasis by inhibiting tumor-associated neutrophils.

Tumor-associated neutrophils (TANs) promote metastasis of multiple cancers, including oral squamous cell carcinoma (OSCC). Melatonin (Mel) reportedly exerts anti-metastatic effects on OSCC. However, little is known about the anti-OSCC effects of Mel involved in TANs. In this study, intensive infiltration of TANs was positively associated with advanced stage, lymphatic metastasis, and poor prognosis of OSCC. Moreover, Mel reduced the survival and migration of OSCC-associated neutrophils. Mechanistically, Mel suppressed the TAN release of C-X-C motif chemokine ligand 8, C-C motif chemokine ligand 2 (CCL2), CCL4, and matrix metalloproteinase-9 by blockage of p38 MAPK and Akt signaling. Mel-fostered TANs decreased the migration and invasion of OSCC cells and reduced tube formation in vitro. Additionally, Mel-hampered pro-motility and pro-angiogenesis effects of TANs were dependent on MMP-9 suppression in OSCC. Overall, The beneficial roles of melatonin in retarding OSCC metastasis were implicated with inhibition of TANs.

RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats.

Major histocompatibility complex class l (MHC I) molecules play a role in determining whether transplanted cells will be accepted or rejected, and masking of MHC I on donor cells has been found useful for immunoprotection of neural xenografts. In the present study, primary human embryonic lung fibroblasts (HELF), HELF treated with lentivirus-mediated small interfering RNAs (siRNAs) targeting human leukocyte antigen A2 (HLA A2, MHC I in humans) (siHELF), and rat embryonic lung fibroblasts (RELF) were stereotaxically grafted into the striatum of 6-hydroxydopamine lesioned rats to explore whether knockdown of HLA A2 could reduce host immune responses against xenografts. Before lentiviral infection, the cells were transduced with retroviruses harboring tyrosine hydroxylase cDNA. Knockdown of HLA A2 protein was examined by Western blotting. The immune responses (the number of CD4 and CD8 T-cells in the brain and peripheral blood), glial reaction, and survival of human fibroblasts were quantitatively evaluated by flow cytometry and immunohistochemistry at 4d, 2w, and 6w post-graft. Animal behaviors were assessed by counting apomorphine-induced rotations pre- and post-grafts. It was shown that a lower level of HLA A2 was observed in siHELF grafts than in HELF grafts, and knockdown of HLA A2 decreased rat immune responses, as indicated by less remarkable increases in the number of CD8 and CD4 T-cells in the brain and the ratio of CD4:CD8 T-cells in the peripheral blood in rats grafted with siHELF. Rats grafted with siHELF exhibited a significant improvement in motor asymmetry post-transplantation and a better survival of human fibroblasts at 2w. The increasing number of activated microglia and the decreasing number of astrocytes were found in three groups of rats post-implantation. These data suggested that RNAi-mediated knockdown of HLA A2 could suppress acute rejection against xenogeneic human cell transplants in the rat brain.

Anaemia and low body mass index are associated with increased cardiovascular disease in patients with Takayasu arteritis.

OBJECTIVES: Despite the high prevalence of cardiovascular disease (CVD) among patients with Takayasu arteritis (TA), few studies have identified its clinical correlates. The aim of this study was to analyse the prevalence of CVD and its association with traditional CV risk factors and disease-related variables in patients with TA. METHODS: A total of 262 consecutive patients with a diagnosis of TA between January 2009 and July 2013 were included in this study. The primary outcome was CVD, defined as the presence of a previous history of myocardial infarction, angina, coronary disease, coronary bypass surgery, coronary angioplasty, and stroke. Multivariate logistic regression analysis was used to determine the relationship of conventional CV risk factors and TA-related variables to the presence of CVD. RESULTS: CVD was present in 64 (24.4%) of patients with TA. Of the total cohort, 16 (6.1%) had a history of myocardial infarction, 31 (11.8%) had angina and 24 (9.2%) had stroke. Multivariate logistic regression analysis revealed that anaemia (OR, 2.449; 95% CI: 1.167-5.141, p=0.018), low body mass index (OR, 0.821; 95% CI: 0.723-0.932, p=0.002), advancing age (OR, 1.050; 95% CI: 1.013-1.088, p=0.007), hyperlipidaemia (OR, 3.792; 95% CI: 1.647-8.727, p=0.002), and family history of CVD (OR, 2.915; 95% CI: 1.188-7.153, p=0.019) were significantly associated with the presence of CVD. CONCLUSIONS: Our study suggests that in addition to traditional CV risk factors, anaemia and low body mass index are independently associated with increased CVD in patients with TA.

Clinical Features and Outcomes of Takayasu Arteritis with Neurological Symptoms in China: A Retrospective Study.

OBJECTIVE: To describe the clinical features and longterm outcomes of patients with Takayasu arteritis (TA) in China who experienced neurological symptoms. METHODS: A retrospective study was undertaken of patients with TA who attended a single study center from 2002 to 2013, who also exhibited neurological symptoms (n = 274). Clinical and imaging features were analyzed, as well as longterm outcomes. RESULTS: The mean age at disease onset was 28.2 ± 11.2 years, with a female-to-male ratio of 4.3:1. The most common neurological manifestation was dizziness (214, 78.1%), the most frequent type of TA was type III (112, 40.9%), and the most common affected artery was the left subclavian (147, 53.6%). Involvement of 3 or 4 branches of the aortic arch was observed in 28% of patients. Among 30 patients experiencing a stroke (10.9%), steno-occlusive lesions of the subclavian artery and common carotid artery were frequently observed in patients with ischemic stroke, while steno-occlusive lesions of the descending aorta, abdominal aorta, and/or renal arteries were more frequently observed with hemorrhagic stroke. Heart failure was the most common cardiovascular event in those who died (n = 6) and in surviving cohorts. CONCLUSION: Neurological features in patients with TA were variable, and correlated with the number of arteries and the site of artery involvement. Resistant hypertension was one of the most important risk factors for hemorrhagic stroke in patients with TA.

HLA-DQA1, DQB1 and DRB1 alleles associated with Takayasu arteritis in the Chinese Han population.

Takayasu arteritis (TA) is a chronic large-vessel vasculitis of unknown etiology. Human leukocyte antigen (HLA) alleles play an important role in the development of TA. Sequence specific primer-polymerase chain reaction was used to detect 10 alleles of the HLA-DQA1 gene and 13 alleles of the HLA-DQB1, -DRB1 gene. A significant increase in the frequencies of DRB1(∗)07 (Pc<0.01, OR=3.44, CI: 2.15-5.52) was observed among TA patients compared with the control group. The significantly increased frequencies of the haplotype DQA1(∗)03:01-DQB1(∗)03:01-DRB1(∗)07 (Corrected P-values<0.01) were observed in TA patients. But in the analysis of clinical manifestations, there are no significant associations with the HLA-DRB1(∗)07 allele.

The association of red blood cell distribution width with anemia and inflammation in patients with Takayasu arteritis.

BACKGROUND: Red blood cell distribution width (RDW) has been shown to be related to both anemia and inflammation in various diseases. However, the role of RDW in patients with Takayasu arteritis (TA) is unknown. Therefore, we investigated the association of RDW with anemia, inflammation, and disease activity in TA. METHODS: RDW was determined in 156 patients with TA and in 156 control subjects. Anemia status and disease activity were defined according to the World Health Organization and National Institutes of Health criteria, respectively. RESULTS: RDW was significantly increased in patients with anemia (14.6±2.2) compared with those without anemia (13.6±1.3, p<0.001) and control subjects (12.7±0.6, p<0.001). Regardless of the presence of anemia, RDW showed correlation with high-sensitivity C-reactive protein (hs-CRP) (both p<0.05). RDW was higher in active TA than inactive TA in patients without anemia (14.1±1.5 vs. 13.3±1.1, p=0.001). Moreover, multiple regression analysis showed that hs-CRP and mean corpuscular volume were independently associated with RDW. CONCLUSIONS: RDW is influenced by both anemia and inflammation, and RDW may be a useful marker to assess disease activity in patients without anemia.

N-terminal Pro-B-type Natriuretic Peptide is Associated with Arterial Stiffness as Measured According to the Brachial-ankle Pulse Wave Velocity in Patients with Takayasu Arteritis.

AIM: Takayasu arteritis (TA) is associated with increased cardiovascular morbidity and mortality, and the degree of arterial stiffness is an independent predictor of cardiovascular mortality in a variety of diseases. In addition, the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, have been found to be higher in patients with TA than in healthy controls. In this study, we aimed to investigate the relationship between the plasma NT-proBNP levels and arterial stiffness in patients with TA. METHODS: Seventy-two patients with TA were recruited in this study. The participants were analyzed with respect to the NT-proBNP levels, cardiovascular risk factors, TA-related variables and arterial stiffness assessed according to the brachial-ankle pulse wave velocity (baPWV). The patients were divided into two groups based on the mean baPWV, and the association between the NT-proBNP and baPWV values was tested using uni- and multivariate analyses. RESULTS: Twenty-four patients (33.3%) were classified into the high-baPWV group. The body mass index (p=0.035), systolic blood pressure (p＜0.001), diastolic blood pressure (p=0.001), mean blood pressure (p＜0.001), plasma NT-proBNP levels (p=0.036) and total cholesterol levels (p=0.030) were significantly higher in the high-baPWV group than in the low-baPWV group. A stepwise multiple linear regression analysis revealed the mean blood pressure (p＜0.001), age (p=0.002), and NT-proBNP level (p=0.002) to be independent determinants of the ba-PWV after adjusting for other confounding factors. CONCLUSIONS: The plasma NT-proBNP levels are independently associated with the degree of arterial stiffness measured according to the baPWV in patients with TA.

Clinical manifestations and longterm outcome for patients with Takayasu arteritis in China.

OBJECTIVE: To describe a large cohort of patients with Takayasu arteritis in China. METHODS: We retrospectively analyzed 566 patients hospitalized in Fuwai Hospital between 2002 and 2013. Data collected were clinical characteristics, laboratory findings, angiographic features, treatment, and longterm outcome. RESULTS: The female to male ratio was 3.8 to 1, and the mean age of onset was 28.9 ± 12.0 years. The most common inflammatory symptom, initial symptom, and coexisting disease were fever (52, 9.2%), dizziness (214, 37.8%), and hypertension (HTN; 392, 69.3%), respectively. Pulmonary artery, coronary artery involvement, and aortic regurgitation were found in 83 (14.7%), 66 (11.7%), and 181 (36.7%) patients, respectively. Elevation of the erythrocyte sedimentation rate was observed in 131 patients (23.1%). Treatment included drugs, interventional therapy, autologous blood vessel transplant, artificial blood vessel transplant, and aortic valve replacement. During a mean followup of 5.0 ± 0.2 years, 32 patients died, including 1 patient who died suddenly during coronary angiography. HTN, major complications, and a progressive disease course were significant prognostic markers. CONCLUSION: HTN, rather than fever, is the leading reason for patients with Takayasu arteritis to see a doctor in China. HTN, major complications, and a progressive disease course are statistically significant predictors of survival. Because of cardiovascular events associated with the disease, early diagnosis and treatment are urgent to improve prognosis.

Function of N-terminal pro-brain natriuretic peptide in Takayasu arteritis disease monitoring.

OBJECTIVE: Increased levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality. Inflammation may also affect levels of NT-proBNP. We investigated the relationship of NT-proBNP with inflammation, disease activity, disease severity, and progression of Takayasu arteritis (TA). METHODS: Plasma levels of NT-proBNP were determined in 68 patients with TA and in 90 control subjects. Disease activity and disease severity in patients with TA were defined according to the National Institutes of Health and Ishikawa's criteria, respectively. RESULTS: NT-proBNP levels were higher in patients with active disease (915.0 ± 328.0 pmol/l) and patients in remission (618.2 ± 243.4 pmol/l) than in controls (427.2 ± 81.4 pmol/l) (p < 0.001). Patients with severe TA showed significantly higher NT-proBNP levels than those with mild-moderate TA (924.0 ± 332.4 pmol/l vs 653.8 ± 269.1 pmol/l; p = 0.001). In patients with longitudinal data, NT-proBNP levels at the active phase were significantly higher than those at the stable phase (944.1 ± 216.7 pmol/l vs 552.1 ± 178.2 pmol/l; p = 0.001). Inflammatory markers, including C-reactive protein, erythrocyte sedimentation rate, and white blood cell count, were independently associated with NT-proBNP levels after adjustment for other confounding factors (R(2) adjusted = 0.307, p = 0.001). CONCLUSION: NT-proBNP levels were significantly increased in patients with active TA exhibiting complications. NT-proBNP levels were independently associated with inflammation. These results indicate that NT-proBNP may be a useful marker to assess the status, severity, and progression of TA.

Subthalamic hGAD65 gene therapy and striatum TH gene transfer in a Parkinson's disease rat model.

The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson's disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death.

Coronary artery involvement in takayasu arteritis in 45 Chinese patients.

OBJECTIVE: We investigated the clinical characteristics, potential difficulties in diagnosis, and therapy for coronary artery involvement in patients with Takayasu arteritis (TA). METHODS: Of 587 consecutive patients hospitalized with TA from 1998 to 2011, those found to have > 50% reduction of diameter of coronary artery by angiography were recruited. We defined the first finding of coronary involvement as baseline. The clinical features, laboratory data, coronary angiographic findings, treatment, and followup outcomes were summarized retrospectively. RESULTS: A total of 45 (7.7%, 45/587) patients with coronary involvement were identified, including 40 with typical angina, and 15 with myocardial infarction. Some had complications such as peripheral vascular murmur, pulseless disease, and hypertension. The average age at onset of cardiac symptoms was 40.3 ± 12.8 years (range 15-64) and 36 were female. At admission, erythrocyte sedimentation rates were elevated in 27 patients (60%) and C-reactive protein levels in 23 (51.1%). The ostia (37.4%) and proximal segments (33.3%) of coronary artery were most frequently involved. The treatment was stent implantation in 10 patients and coronary artery bypass grafting in 13. One female patient suffered sudden death during the angiography. During a mean followup of 5.8 ± 4.5 years, 8 patients died. CONCLUSION: Coronary artery involvement in TA that leads to cardiovascular events, especially to cardiovascular death, is not rare. Early diagnosis and therapy should be emphasized.