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Osteoporosis is a systemic and metabolic bone disease. New drugs with good curative effect, fewer side effects, and high safety need to be developed urgently. Recently, simvastatin has been used to treat osteoporosis more frequently; however, its clinical effect and treatment mechanism are still unknown. With the use of animal models, the treatment effectiveness of simvastatin on experimental osteoporosis was investigated and the functional mechanism was preliminarily explored. The results show that simvastatin significantly increased the mechanical parameters such as maximum load, stiffness, and energy-absorbing capacity, and improved the microarchitecture. They indicated that the antiosteoporosis activity of simvastatin may be due to the promotion of proliferation and differentiation of osteoblasts. Simvastatin was effective in treating experimental osteoporosis. This study provides necessary experimental evidence for the clinical application of simvastatin in osteoporosis treatment.

The use of transgenic plants in agriculture provides many economic benefits, but it also raises concerns over the potential impact of transgenic plants on the environment. We here examined the impact of transgenic high-methionine soybean ZD91 on the arbuscular mycorrhizal (AM) fungal community structure in rhizosphere soil. Our investigations based on clone libraries were conducted in field trials at four growth stages of the crops each year from 2012 to 2013. A total of 155 operational taxonomic units (OTUs) of AM fungi were identified based on the sequences of small subunit ribosomal RNA (SSU rRNA) genes. There were no significant differences found in AM fungal diversity in rhizosphere soil during the same growth stage between transgenic soybean ZD91 and its non-transgenic parental soybean ZD. In addition, plant growth stage and year had the strongest effect on the AM fungal community structure while the genetically modified (GM) trait studied was the least explanatory factor. In conclusion, we found no indication that transgenic soybean ZD91 cultivation poses a risk for AM fungal communities in agricultural soils.

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.

Objectives: Patients with non-small-cell lung cancer (NSCLC) develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) after tumor regression. No approved targeted therapies are currently available after initial EGFR TKI treatment. This study investigated the efficacy of continuing EGFR TKI therapy with local treatments for patients with NSCLC and local progression or minimal/slow progression on TKI therapy., Materials and Methods: Fifty-five patients with NSCLC treated with EGFR TKIs and developed acquired resistance to the drug were included. Initial response to target therapy, median progression free survival (PFS1), progression pattern, and first progression site were assessed. Median progression free survival to physician assessment progression (PFS2) and difference between PFS1 and PFS2 (PFS difference) were also recorded., Results and Conclusion: PFS1 was 11.2 months, PFS2 was 20.3 months, and PFS difference was 8.3 months. Nineteen patients (34.5%) who manifested progression received local therapy, and 16 (28.6%) underwent rebiopsy after progression with six positive EGFR T790M mutations detected. Cox proportional hazards regression model showed that only the first line of treatment was significantly correlated with PFS difference. NSCLC patients with acquired resistance to EGFR TKIs could benefit from the same TKI therapy through months to years of disease control.

Heng-Gu-Gu-Shang-Yu-He-Ji, also known as OsteoKing, is used as a herbal Traditional Chinese Medicine for the treatment of bone disease, including femoral head necrosis and osteoarthritis. However, whether OsteoKing has anti-osteoporotic properties has remained to be elucidated. The purpose of the present study was therefore to investigate the effects of OsteoKing on ovariectomy-induced osteoporosis in rabbits. Female New Zealand white rabbits were randomly divided into an ovariectomized (OVX) group and a sham-surgery group. The rabbits in the OVX group were subjected to an ovariectomy, while the rabbits in the sham group were subjected to the removal of an area of fat near the two ovaries. Bone mineral density, mechanical properties, serum biochemical parameters and micro-architecture were examined at 150 days post-OVX to characterize the experimental animal model. Once the osteoporotic rabbit model had been established, the rabbits in the OVX group were divided into the following groups: Model group, nilestriol group and 300 and 600 mg/kg OsteoKing groups, containing 16 rabbits in each group. OsteoKing and nilestriol were administered orally. The bone mineral density, mechanical properties, serum biochemical parameters, histology and micro-architecture were examined using dual-energy X-ray absorptiometric analysis, mechanical assessments, enzyme-linked immunosorbent assays, histopathological evaluation and micro-computerized tomography examination following 60 days and 120 days of treatment, respectively. Treatment with OsteoKing led to an elevation in the bone mineral density of the vertebra and serum phosphorus levels, reduced serum concentrations of osteocalcin, procollagen type I N-terminal peptide, tartrate-resistant acid phosphatase 5b and cross-linked N-telopeptide of type I collagen, improved mechanical properties (maximum load, stiffness and energy absorption capacity), and micro-architecture of the lumbar vertebra in the OVX osteoporotic rabbit model following treatment for 120 days. In conclusion, it was demonstrated that OsteoKing is effective in the prevention of estrogen deficiency-associated bone loss and may be a promising drug for the treatment of post-menopausal osteoporosis.

Bevacizumab (Bev), a monoclonal antibody against vascular endothelial growth factor, when combined with standard first-line chemotherapy, shows impressive clinical benefit in advanced non-squamous non-small cell lung cancer (ns-NSCLC). Our study aims to investigate whether the addition of Bev to pemetrexed improves progression-free survival (PFS) in advanced ns-NSCLC patients after the failure of at least one prior chemotherapy regimens. Patients with locally advanced, recurrent, or metastatic ns-NSCLC, after failure of platinum-based therapy, with a performance status 0 to 2, were eligible. Patients received 500 mg/m(2) of pemetrexed intravenously (IV) day 1 with vitamin B12, folic acid, and dexamethasone and Bev 7.5 mg/kg IV day 1 of a 21-day cycle until unacceptable toxicity, disease progression or the patient requested therapy discontinuation. The primary end point was PFS. Between December 2011 and October 2013, 33 patients were enrolled, with median age of 55 years and 36.4% men. Twenty-three patients (69.7%) had received two or more prior regimens, and 28 patients (84.8%) had received chemotherapy containing pemetrexed. The median number of the protocol regimens was 4. Median PFS was 4.37 months (95% CI 2.64-6.09 months). Median overall survival (OS) was 15.83 months (95% CI 10.52-21.15 months). Overall response rates were 6.45%. Disease control rate was 54.84%. No new safety signals were detected. No patient experienced drug-related deaths. The combination of Bev and pemetrexed every 21 days is effective in ns-NSCLC patients who failed of prior therapies with improved PFS. Toxicities are similar with historical data of these two agents and are tolerable. Our results may provide more a regimen containing Bev and pemetrexed for Chinese clinical practice in previously treated ns-NSCLC.

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.

Objective: To evaluate efficacy and outcome of endovascular therapy for complex arteriosclerosis obliterans of the lower extremities., Methods: In this single-center retrospective study, the clinical data of consecutive 114 cases with TASC II type C/D lower extremity obstructive disease and clinical stage of Fontaine ≥ IIb and ankle brachial index <0.9 underwent endovascular therapy from December 2011 to January 2013 were collected. Telephone or clinic interviews were conducted to investigate the clinical outcomes., Results: There were 39 TASC II type C patients and 75 TASC II type D patients, 78 patients were in Fontaine IIb, 30 patients in Fontaine III and 6 patients in Fontaine IV stages. Immediate procedural success rate was 94.9% (131/138). Ankle brachial index was increased from 0.54 ± 0.26 at baseline to 0.83 ± 0.30 at discharge (P < 0.01). No adverse event was observed during the perioperative period. During (15.7 ± 8.7) months follow-up, cumulative patency rate of 6, 12 and 18 months was 75.8% (94/124) , 68.7% (68/99) and 39.2% (20/51) respectively and limb salvage rate was 100%., Conclusion: Endovascular therapy for complex arteriosclerosis obliterans of the lower extremities is effective and safe.

Objective: The aim of this study was to evaluate the safety and efficacy of percutaneous transluminal angioplasty (PTA) for symptomatic pulmonary stenosis in Takayasu arteritis (TA)., Methods: From January 2009 to December 2012, clinical data of 14 patients [mean age 33.9 ± 9.3 yrs; 11 patients female (78.6%)] with symptomatic pulmonary stenosis in TA underwent PTA and were analyzed prospectively., Results: PTA was successfully performed in 22 lesions of 14 patients. Among those lesions, 18 were treated by PTA alone while the others were treated with stent implantation. Three patients (21.4%) had reperfusion pulmonary injury; 2 patients recovered completely while the other died of respiratory failure 3 days after the procedure. Mean pulmonary arterial pressure (PAP) decreased from 53.4 ± 15.8 mmHg to 38.4 ± 12.7 mmHg immediately after intervention (p < 0.001). After an average of 29 months of followup, the New York Heart Association functional class and 6-min walking distances improved while mean PAP measured by echocardiography decreased significantly (compared with baseline, all p < 0.01). One patient died of severe pulmonary infection and cardiac shock at 28 months after the procedure., Conclusion: The study showed that PTA improved subjective symptoms and objective variables of the patients with symptomatic pulmonary stenosis in TA, with an acceptable mortality. PTA may be a promising therapeutic strategy for symptomatic pulmonary stenosis in TA.

Previous studies have shown that methionine from root exudates affects the rhizosphere bacterial population involved in soil nitrogen fixation. A transgenic line of Zigongdongdou soybean cultivar (ZD91) that expresses Arabidopsis cystathionine γ-synthase resulting in an increased methionine production was examined for its influence to the rhizosphere bacterial population. Using 16S rRNA gene-based pyrosequencing analysis of the V4 region and DNA extracted from bacterial consortia collected from the rhizosphere of soybean plants grown in an agricultural field at the pod-setting stage, we characterized the populational structure of the bacterial community involved. In total, 87,267 sequences (approximately 10,908 per sample) were analyzed. We found that Acidobacteria, Proteobacteria, Bacteroidetes, Actinobacteria, Chloroflexi, Planctomycetes, Gemmatimonadetes, Firmicutes, and Verrucomicrobia constitute the dominant taxonomic groups in either the ZD91 transgenic line or parental cultivar ZD, and that there was no statistically significant difference in the rhizosphere bacterial community structure between the two cultivars.

Objective: As a novel device-based approach targeting the renal sympathetic nerves, renal denervation has been shown to be effective and safe in reducing blood pressure. The femoral artery is currently the most common access site for this procedure due to catheter profile and length limitations that restrict the use of radial access. The purpose of this study was to evaluate technical feasibility and short-term outcomes of transradial renal denervation by a longer radiofrequency ablation catheter (155 cm; AngioCare)., Methods: Five patients (mean age, 46 ± 15 years; 3 male) with resistant hypertension underwent successful transradial renal denervation (3 right, 2 left) at our institution from April to June, 2013. In this group, 3 patients were excluded from femoral access due to an acute aorto-renal angle, or severe tortuosity of the abdominal aorta and iliac arteries. All 5 patients were followed at 1 month and 3 months post procedure. Blood pressure, use of antihypertensive agents, renal function, and complications were investigated., Results: The mean reduction of 24-hour ambulatory blood pressure was -13/-8 mm Hg at 1-month and -20/-12 mm Hg at 3-month follow-up exam (P<.05, compared with baseline) with unchanged antihypertensive drugs. There was no significant change of renal function at 3-month follow-up exam (P>.05, compared with baseline). No complications were observed in this patient group., Conclusions: Our preliminary results revealed that transradial renal denervation is technically feasible, relatively safe, and effective for the treatment of resistant hypertension, especially where a femoral approach may not be possible.

Background: As a novel device-based approach targeting the renal sympathetic nerves, percutaneous renal denervation (RDN) has been shown to be effective and safe for reducing blood pressure. However, while considerable data on RDN have been obtained from Western populations, there is limited findings from East Asian populations. The purpose of this study was to evaluate one-year outcomes of RDN for the treatment of resistant hypertension in Chinese patients., Methods: Between February and August 2012, 14 patients (mean age 39 ± 8 years, 10 males) with resistant hypertension underwent successful RDN at the Fuwai Hospital. All 14 patients were followed up at 1, 3, 6 and 12 months post-procedure. Blood pressure, use of antihypertensive agents, renal function, and complications were investigated., Results: Baseline values included mean office blood pressure of 164/103 ± 14/10 mmHg, mean 3.9 ± 0.6 anti-hypertensive agents, and an estimated glomerular filtration rate of (79 ± 19) ml × min(-1)×1.73 m(-2). Office blood pressure after the procedure was reduced by -14/-10, -17/-11, -21/-12, and -24/-14 mmHg at 1, 3, 6, and 12 months respectively, and the reduction of the number of antihypertensive agents at the above corresponding time points was -1.3, -1.5, -1.7 and -1.8 respectively (all P < 0.001). The mean reduction of 24-hour ambulatory blood pressure was similar to the reduction of office blood pressure at the four corresponding time points. Renal function did not significantly change at any time point (all P > 0.05). No clinical complications were observed at 12-month follow-up., Conclusion: This study showed that RDN seems to be effective in reducing blood pressure of Chinese patients with resistant hypertension, with minimal adverse events at 12-month follow-up.

Syphilis is a chronic infection caused by Treponema pallidum subsp. pallidum, and diagnosis with sensitive and specific methods is a challenging process that is important for its prevention and treatment. In the present study, we established a recombinant protein TpF1-based indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and a Western blot assay for human and rabbit sera. The 20-kDa recombinant protein TpF1 was detected by Western blotting performed with sera from rabbits immunized with recombinant TpF1 and infected with the T. pallidum Nichols strain and T. pallidum clinical isolates but was not detected by Western blotting with sera from uninfected rabbits. The sensitivity of the recombinant protein was determined by screening sera from individuals with primary, secondary, latent, and congenital syphilis (n = 82). The specificity of the recombinant protein was determined by screening sera from uninfected controls (n = 30) and individuals with potentially cross-reactive infections, including Lyme disease (n = 30) and leptospirosis (n = 5). The sensitivities of TpF1-based ELISAs were 93.3%, 100%, 100%, and 100% for primary, secondary, latent, and congenital syphilis, respectively, and the specificities were all 100% for sera from uninfected controls and individuals with potentially cross-reactive infections. In Western blot assays, the sensitivities and specificities of TpF1 for human sera were all 100%. The reactivities of TpF1 with syphilitic sera were proportional to the titers of the T. pallidum particle agglutination (TPPA) assay. These data indicate that the recombinant protein TpF1 is a highly immunogenic protein in human and rabbit infections and a promising marker for the screening of syphilis.

Heme oxygenase-1 (HO-1) is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury and performs a vital function in the maintenance of cell hemostasis. Increasing numbers of reports have indicated that mycoplasma-derived membrane lipoproteins/lipopeptides, such as macrophage-activating lipopeptide-2 (MALP-2), function as agents that stimulate the immune system by producing various inflammatory mediators, such as cytokines and cyclooxygenase 2 (COX-2), which play roles in the pathogenesis of inflammatory responses during mycoplasma infection. Here, we report that MALP-2 induced HO-1 mRNA and protein expression and upregulated HO-1 enzyme activity in THP-1 cells. Specific inhibitors of mitogen-activated protein kinases (MAPKs), SB203580, PD98059, and SP600125, significantly abolished HO-1 expression. In addition, MALP-2 also induced NF-E2-related factor 2 (Nrf2) translocation, and the silencing of Nrf2 expression in THP-1 cells decreased the levels of MALP-2-mediated HO-1 expression. Furthermore, COX-2 protein expression levels were upregulated in THP-1 cells in response to MALP-2, and transfection with small interfering RNAs of HO-1 significantly increased COX-2 accumulation. These results demonstrate that MALP-2 induces HO-1 expression via MAPKs and Nrf2 pathways and, furthermore, that MALP-2-induced COX-2 expression was modulated by HO-1 in THP-1 cells.

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.

Background: Targeted therapy in non-small cell lung cancer (NSCLC) had become a research hotspot. Both of gefitinib and erlotinib had already been recommended as first line treatment in epidermal growth factor receptor (EGFR) mutant advanced NSCLC patients. The study aimed to compare the effectiveness and prognosis of advanced NSCLC with gefitinib or erlotinib, as well as the cost-effectiveness ratio of the two drugs., Methods: Data of 66 EGFR mutant NSCLC patients who were included in Guangzhou medical insurance were analyzed. The efficacy and adverse reactions were evaluated. All the patients were followed-up regularly and the cost of the treatment was recorded., Results: The median progression free survival (PFS) of all patients was 15.0 months. 49 patients received gefintib and 17 patients had erlotinib. The PFS for the two groups of patients was 17.5 month and 13 months, respectively (P=0.459). 31 (62.3%) patients had rash in gefitinib group, 16 (94.1%) in erlotinib group. Cost-effectiveness ratio (CER) in gefitinib group was 3,027 RMB per month, while 6,800 RMB in erlotinib group. The incremental cost-effectiveness ratio (ICEA) of erlotinib was 2.25 times of gefitinib., Conclusions: For EGFR mutant advanced NSCLC patients, equal efficacy and survival benefit were observed in patients with gefitinib and erlotinib. The adverse reaction was milder in gefitinib group than that of erlotinib group. And with Guangzhou medical insurance, gefitinib had a superior cost-effectiveness ratio.

Chronic neuropathic pain is a common and debilitating consequence of spinal cord injury (SCI). In a rat contusion injury model, we observed that chronic neuropathic pain is present on day 7 after SCI and persists for the entire 56-day observation period. However, currently available pain therapies are inadequate for SCI-induced neuropathic pain. In this study, we show that spinal transplantation of mouse embryonic stem cell-derived oligodendrocyte progenitor cells (OPCs) enhances remyelination in the injured spinal cord and reduces SCI-induced chronic neuropathic pain. Moreover, we found that SCI reduces the protein level of neuregulin-1 and ErbB4 in the injured spinal cord and that OPC transplantation enhances the spinal expression of both proteins after SCI. Finally, intrathecal injection of neuregulin-1 small interfering RNA, but not the control nontarget RNA, diminishes OPC transplantation-produced remyelination and reverses the antinociceptive effect of OPC transplantation. Our findings suggest that the transplantation of embryonic stem cell-derived OPCs is an appropriate therapeutic intervention for treatment of SCI-induced chronic neuropathic pain, and that neuregulin-1/ErbB signaling plays an important role in central remyelination under pathological conditions and contributes to the alleviation of such pain., (Copyright © 2012 AlphaMed Press.)

Objective: The study is to observe the effect of nitric oxide (NO) donor and scavenger to the hypoglossal motor nucleus (HMN) activity and explore the underlying mechanism., Methods: Male adult anesthetized Wistar rats were anesthetized. The activity of genioglossus (GG), diaphragma, blood pressure (BP) and respiratory rate (RR) were recorded when constant microdialysis perfusion of artificial cerebrospinal fluid (ACSF) to HMN as control, followed with diethylamine NONOate sodium salt hydrate (DEA), a NO donor, and 2-(4-carboxyphenyl)-4,4,5,5-tetra-methylimidazoline-1-oxyl-3-oxide potassium salt (carboxy-PTIO), a NO scavenger., Results: Compared with ACSF, application of DEA and carboxy-PTIO at HMN increased and decreased the GG activity respectively and significantly (P<0.05), mainly respiratory-related activity. The tonic GG, diaphragma activity, BP and RR had not been affected statistically between 30-120 min when microdialysis perfusion of both DEA and carboxy-PTIO were delivered., Conclusion: Acting as an excitatory neurotransmitter of HMN, NO may contribute to the patency of upper airway physiologically.

A contusive model of spinal cord injury at spinal segment T8-9 was established in rats. Huantiao (GB30) and Huatuojiaji (Ex-B05) were punctured with needles, and endogenous neural stem cells were labeled with 5-bromo-2'-deoxyuridine (BrdU) and NG2. Double immunofluorescence staining showed that electroacupuncture markedly increased the numbers of BrdU(+)/NG2(+) cells at spinal cord tissue 15 mm away from the injury center in the rostral and caudal directions. The results suggest that electroacupuncture promotes the proliferation of endogenous neural stem cells and oligodendrocytes in rats with spinal cord injury.

The authors report, to the best of their knowledge, the first case of a spontaneous tension pneumocephalus with subcutaneous emphysema. Hyperpneumatization of the cranium and mechanical compression contributed jointly to the formation of a fistula, and air pressure caused a subsequent disruption of the suture and air leakage into the subcutaneous space. A minimally invasive otological procedure proved efficacious for resolution.

Cardiac hypertrophy is frequently caused by pressure overload (i.e., high blood pressure or hypertension) and can lead to heart failure. The major objective of the present study was to investigate the proteomic changes in response to the development of left ventricular hypertrophy (LVH) induced by abdominal aortic banding (AB) and its prevention by antihypertensive treatment with angiotensin II receptor blocker (ARB) telmisartan. One week after AB and Sham surgery, rats were assigned into three groups: SHAM-control, aortic banding without treatment (AB-Ctrl) and aortic banding with telmisartan treatment (AB-Telmi; 5mg/kg/day for 8 weeks). Echocardiography, hemodynamics, and pathology were performed to assess LVH. Left ventricular myocardium was sampled. The analysis of proteomic proteins from myocardium was performed by two-dimensional gel electrophoresis and MALDI-TOF-MS. In AB-Ctrl, heart rate, systolic arterial blood pressure, diastolic blood pressure, left ventricular end systolic pressure, interventricular septal thickness at diastole, posterior wall thickness in diastole, heart weight (HW) and HW/body weight (BW) were increased, indicating that both hypertension and LVH developed. Telmisartan prevented hypertension and LVH. Concurrently, among numerous proteins, there were 17 that were differentially expressed among hypertrophic hearts, normal hearts, and the hearts where hypertrophic response was suppressed by ARB treatment. Primarily, proteins involved in cell structure, metabolism, stress and signal transduction exhibited up-regulations in LVH, providing cellular and molecular mechanism for hypertrophic development. These changes were prevented or greatly attenuated by telmisartan regimen. Interestingly, antioxidative-related heat shock protein 2 was detected neither in SHAM-Ctrl nor in AB-Ctrl, but in AB-Telmi. LVH is accompanied by series changes of protein expression. Both LVH and proteomic changes can be prevented by blockade of renin-angiotensin system with telmisartan. These protein alterations may constitute mechanistic pathways leading to hypertrophy development and experimental targets for novel therapeutic strategy.

The theoretical operation and experimental demonstration of a Fourier transform imaging spectropolarimeter for real time measurement of the polarization state of light are presented. The spectropolarimeter uses a Wollaston prism as a birefringent interferometer and two high-order retarders to incorporate channeled polarimetry. Compared with previous instruments, the most significant advantage of the described model is that the complete wavelength-dependent polarization is acquired simultaneously along a one-dimensional spatial image by a single snapshot. Also, we show that, in this configuration, we can benefit from the advantages of the model: it is compact and robust, and the birefringent interferometer has a high throughput.

Background: The prevalence and clinical significance of orthostatic hypertension (OHT) remain largely undetermined in hypertensive patients. This study investigated the association of OHT and orthostatic hypotension (OH) with cardiovascular disease (CVD) and target organ damage (TOD) in hypertensive patients., Methods: A cross-sectional study was conducted in 4,711 hypertensives and 826 normotensives, aged 40-75 years. OHT was defined as an increase in systolic blood pressure (SBP) of > or =20 mm Hg, and OH was defined as either a reduction in SBP of at least 20 mm Hg or a reduction in diastolic BP (DBP) of at least 10 mm Hg during the first 3 min after standing., Results: Hypertension was only independently associated with a risk of OHT. After controlling for age, sex, and other confounders, OH was associated with peripheral artery disease (PAD) (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.15-1.89, P < 0.01), left ventricular hypertrophy (LVH) (OR 1.48, 95% CI 1.12-1.93, P < 0.001), coronary artery disease (CAD) (OR 1.71, 95% CI 1.12-2.61, P < 0.01), and stroke (OR 1.72, 95% CI 1.19-2.34, P < 0.01), but OHT was only associated with PAD (OR 1.36, 95% CI 1.05-1.81, P < 0.05) and stroke (OR 1.76, 95% CI 1.27-2.26, P < 0.01). The adjusted OR for PAD, predicted by the quintiles of the orthostatic SBP changes, showed a J-shaped relationship in untreated hypertensive patients, as was also the case for LVH in hypertensive women., Conclusions: OH is associated with CV risk; the associations of OHT with TOD and stroke in hypertensive patients still need to be confirmed in prospective studies.

Background: Sex-specific responses to antihypertensive drugs are not very well understood., Objective: To investigate sex-related differences in blood pressure response to antihypertensive drugs in a community-based prospective clinical trial., Methods: We recruited 3535 untreated hypertensive patients (2326 women), aged 40-75 years, from 7 rural communities in China. Subjects were randomized to 1 of 4 drug groups: atenolol, hydrochlorothiazide (HCTZ), captopril, or sustained-released nifedipine; duration of the study was 8 weeks. Mean blood pressure reduction, blood pressure control rates, and frequency of adverse events were compared between men and women., Results: Women had a better response to HCTZ in relation to diastolic blood pressure (1.8 mm Hg lower) than did men (p < 0.05) and were 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). In the atenolol group, mean systolic blood pressure decreased 3.9 mm Hg more in women than in men (p < 0.05), and women were 65% more likely to reach the control goal of systolic blood pressure and 57% more likely to reach the control goal of diastolic blood pressure than were men (p < 0.05). Significant sex-related differences were also found in drug-related adverse events in the nifedipine group (15.8% in women vs 9.8% in men; p = 0.017) and in the captopril group (14.3% in women vs 8.4% in men; p = 0.005), but no differences were seen with HCTZ or atenolol., Conclusions: Women have better blood pressure responses to HCTZ and atenolol and experience more adverse effects with sustained-release nifedipine and captopril than do men, indicating that sex should be taken into account when selecting antihypertensive drugs.

Objective: Liddle syndrome is a rare autosomal-dominant monogenic form of hypertension caused by mutations in the C-termini of the epithelial sodium channel beta- or gamma-subunit encoded by SCNN1B and SCNN1G, respectively, and often presenting with a familial history of hypertension. The purpose of this study was to determine whether mutations of SCNN1B or SCNN1G were present in a patient clinically suspected to have Liddle syndrome with no familial history of hypertension., Design and Patients: We screened the C-terminus of SCNN1B and SCNN1G in the patient, and also screened for the mutation in his parents, 50 hypertensive patients and 50 controls., Results: In this patient, no mutations were found in the C-terminus of SCNN1B. However, we found a frameshift mutation caused by an 'AGCTC' deletion at the 583 codon in SCNN1G. The frameshift resulted in a new termination site at the 585 codon of the gamma-subunit and the deletion of its PY motif. Neither his parents nor 50 randomly selected patients with hypertension nor 50 controls have the mutation, indicating that this is a de novo mutation and not a common genetic polymorphism., Conclusion: The de novo mutation is the first reported frameshift of the gamma-subunit causing Liddle syndrome. These data imply that a familial history of hypertension is not an essential criterion for the diagnosis of Liddle syndrome.

Objectives: Peripheral arterial disease (PAD) is associated with morbidity and mortality of coronary heart disease and stroke. Hypertension is an independent risk factor for peripheral arterial disease. However, the prevalence and risk factors of PAD in hypertensive patients have not been studied in China., Methods: In order to investigate the prevalence of PAD and its risk factors in China, a cross-sectional study was carried out. A total of 4716 patients with hypertension and 833 age-gender matched people without hypertension were recruited; age 40 to 75 years, from seven rural communities. PAD was defined as an ankle-brachial index (ABI) or=140 mm Hg, diastolic blood pressure >or=90 mm Hg, or history of antihypertensive drug use., Results: The prevalence of PAD is 8.7% (n = 408) in patients with hypertension (n = 4716), higher than in people without hypertension (5.0%, n = 833, P = .004). Hypertensive patients with PAD were older, (61 +/- 8.6 vs 58 +/- 8.6, P < .01), had more conventional cardiovascular risk factors including systolic blood pressure (170 +/- 22.6 vs 167 +/- 22.7, P < .01), pulse pressure (72 +/- 19.7 vs 68 +/- 18.9, P < .01), blood glucose (5.8 +/- 2.2 vs 5.6 +/- 1.7, P < .05), total cholesterol (5.7 +/- 1.3 vs 5.5 +/- 1.1, P < .05), and serum uric acid (355 +/- 98.0 vs 293 +/- 86.2, P < .05) than the hypertensive patients without PAD. After adjusting for gender, age, and other cardiovascular risk factors by using multiple logistical regression analysis, PAD was still associated with current smoking (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.29), history of stroke (OR = 1.50, 95% CI 1.12-2.00), serum uric acid (OR = 1.21, 95% CI 1.10-1.59), and total cholesterol (OR = 1.12, 95% CI 1.10-1.59)., Conclusion: This study reports, for the first time, the prevalence of PAD in Chinese patients with hypertension, which is quite different from that in westerners, and that PAD is independently associated with conventional cardiovascular risk factors.

Objective: To demonstrate the alterations of Protein Kinase C epsilon (PKC epsilon) and components of its signaling complexes after treatment with fosinopril and carvedilol and analyze potential molecular mechanisms of the two drugs for cardiac hypertrophy and heart failure., Methods: Pressure-overload cardiac hypertrophy (POH) was developed in 8-week-old male Sprague Dawley rats by abdominal aortic banding. The rats were divided into three groups at the age of 20 weeks: POH without failure group, reversed POH with drugs group, and POH with failure group on high diet. Western Blot analysis, co-immunoprecipitation and proteomic analysis were performed in ventricular tissues of rat hearts., Results: Increased PKC epsilon was found during POH. PKC epsilon decreased during transition from POH to heart failure (HF). However, increased PKC epsilon inclined to recover to normal levels after treatment with both drugs. There were differential proteins in PKC epsilon complexes during the different stages of POH. The two significant PKC epsilon-binding proteins, MAD1 and Lyn A, were only present in PKC epsilon complex during reversing POH with drugs., Conclusion: Chronic administration of carvedilol and fosinopril could reverse the development of POH and delay the appearance of HF, partly by regulating PKC epsilon level and its signaling complex. MAD1 and Lyn A may be important proteins participating in the reversing process.

Background: The haplotypes in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) have been found to affect warfarin dose response through effects on the formation of reduced-form vitamin K, a cofactor for gamma-carboxylation of vitamin K-dependent proteins, which is involved in the coagulation cascade and has a potential impact on atherosclerosis. We hypothesized that VKORC1-dependent effects on the coagulation cascade and atherosclerosis would contribute to susceptibility for vascular diseases., Methods and Results: To test the hypothesis, we studied the association of polymorphisms of VKORC1 with stroke (1811 patients), coronary heart disease (740 patients), and aortic dissection (253 patients) compared with matched controls (n=1811, 740, and 416, respectively). Five common noncoding single-nucleotide polymorphisms of VKORC1 were identified in a natural haplotype block with strong linkage disequilibrium (D'>0.9, r2>0.9), then single-nucleotide polymorphism (SNP) +2255 in the block was selected for the association study. We found that the presence of the C allele of the +2255 locus conferred almost twice the risk of vascular disease (odds ratio [OR] 1.95, 95% confidence interval [CI] .58 to 2.41, P<0.001 for stroke; OR 1.72, 95% CI 1.24 to 2.38, P<0.01 for coronary heart disease; and OR 1.90, 95% CI 1.04 to 3.48, P<0.05 for aortic dissection). We also observed that subjects with the CC and CT genotypes had lower levels of undercarboxylated osteocalcin (a regulator for the bone), probably vascular calcification, and lower levels of protein induced in vitamin K absence or antagonism II (PIVKA-II, a des-gamma-carboxy prothrombin) than those with TT genotypes., Conclusions: The haplotype of VKORC1 may serve as a novel genetic marker for the risk of stroke, coronary heart disease, and aortic dissection.

Objectives: To evaluate the safety and short-term efficacy of stent revascularization as treatment for renal artery stenosis., Methods: Percutaneous transluminal renal angioplasty with stent (PTRAS) was performed on 30 consecutive patients with severe renal artery stenosis for poorly controlled hypertension or preservation of renal function. They subsequently underwent 3-month clinical follow-up for the effect of the procedure on renal function, blood pressure control and the number of antihypertensive medications used., Results: Angiographic success was obtained in 29 (96.7%) of the 30 patients after PTRAS. 3 months after the procedure systolic and diastolic blood pressures significantly decreased (from 173.5 to 135.8 mm Hg and from 95.8 to 75.6 mm Hg, respectively; P < 0.001) and less antihypertensive medications were taken (from 2.5 to 1.5). Blood pressure in 5 (16.7%) of the 30 patients became normal without taking any antihypertensive medication and blood pressure control was more facile in 22 (73.3%) of the patients. However, there was no improvement in 3 (10.0%) of the patients. Creatinine slightly decreased in 2 (6.7%) of the 30 patients and remained stable in 28 (93.3%) of the 30 patients. There was no statistical significance in this respect., Conclusions: Renal artery stent revascularization has a short-term beneficial effect on blood pressure control and a nondeleterious effect on renal function. The long-term efficacy should be investigated. The procedure is safe in usual.