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The rising prevalence of cardiovascular disease has become a global health concern. The occurrence of cardiovascular disease is the result of long-term interaction of many risk factors, one of which is diabetes. As a novel anti-diabetic drug, DPP4 inhibitor has been proven to be cardiovascular safe in five recently completed cardiovascular outcome trials. Accumulating studies suggest that DPP4 inhibitor has potential benefits in a variety of cardiovascular diseases, including hypertension, calcified aortic valve disease, coronary atherosclerosis, and heart failure. On the one hand, in addition to improving blood glucose control, DPP4 inhibitor is involved in controlling cardiovascular risk factors. On the other hand, DPP4 inhibitor directly regulates the occurrence and progression of cardiovascular diseases through a variety of mechanisms. In this review, we summarize the recent advances of DPP4 in cardiovascular disease, aiming to discuss DPP4 inhibitor as a potential option for cardiovascular therapy.

IntroductionProvisional stenting using drug-eluting stent is effective for simple coronary bifurcation lesions. Kissing balloon inflation using conventional non-compliant balloon is the primary treatment of side branch (SB) after main vessel (MV) stenting. Drug-coating balloon (DCB) is reported to be associated with less frequent clinical events in in-stent restenosis and small vessel disease. The importance of DCB in bifurcation treatment is understudied. Accordingly, this trial is designed to investigate the superiority of DCB to non-compliant balloon angioplasty for SB after provisional stenting in patients with true coronary bifurcation lesions.Methods and analysisThe DCB-BIF trial is a prospective, multicentre, randomised, superiority trial including 784 patients with true coronary bifurcation lesions. Patients will be randomised in a 1:1 fashion to receive either DCB or non-compliant balloon angioplasty if SB diameter stenosis >70% after MV stenting. The primary endpoint is the composite of major adverse cardiac event at the 1-year follow-up, including cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularisation. The major secondary endpoints include all-cause death, periprocedural MI, spontaneous MI, clinically driven target vessel revascularisation, in-stent restenosis, stroke and individual component of the primary endpoint. The safety endpoint is the risk of stent thrombosis.Ethics and disseminationThe study protocol and informed consent have been reviewed and approved by the Institutional Review Board of all participating centres. The written informed consent for participation in the trial will be obtained from all participants. The results of this study will be published in a peer-reviewed journal and disseminated at conferences.Trial registration numberNCT04242134.

Background and purpose To evaluate the application of treatment planning system (TPS) assisted large-aperture computed tomography (CT) simulator in percutaneous biopsy, and report our initial experience of the accuracy and safety of this procedure.Methods From November 2018 to December 2019, treatment planning system assisted large-aperture CT simulator guided percutaneous biopsy was performed on 38 cases, with 34 of percutaneous lung biopsy, three of abdominal lesions biopsy, and one case of deep supraclavicular lymph node biopsy. The major results including planned and actual puncture parameters, the success rate, pathological information and complications were recorded. The analyses of puncture accuracy were accomplished by pared-t test and Wilcoxon rank sum test. And the risk factors of puncture accuracy and complications were further identified.Results The entire cohort achieved one-time success of biopsy. No significant differences were presented between planned and actual puncture depth and direction (P = 0.436 and 0.382), indicating the precision of the process. And the pulmonary puncture location was related to the accuracy of puncture direction (P = 0.033). Biopsy specimens were successfully obtained in 38 cases. The diagnostic rate of malignancy was 76%, of which 80% for initial treatment group and 69% for treated group, respectively. For patients with pulmonary biopsy, 12 had minor pneumothorax and 2 progressed to massive pneumothorax. Only three cases suffered needle track bleeding, and no other complications were observed. Additionally, the regression analysis found a significant correlation between puncture angle and the incidence of pneumothorax (P = 0.027).Conclusions TPS assisted large-aperture CT simulator improved the procedure of percutaneous biopsy by combining the advantages of radiotherapy specialty. The initial results suggested the increase of puncture accuracy and success rate, with satisfactory safety simultaneously. It might offer new insights into the field of CT-guided percutaneous biopsy.

To investigate the association between anxiety disorders and left ventricular hypertrophy in patients with essential hypertension.Left ventricular structure and function were assessed with echocardiography in 56 patients with essential hypertension and anxiety disorder (study group) and in 56 patients with hypertension only (control group). Serum adrenomedullin levels were also measured in these patients.There was no statistically significant difference in the left ventricular ejection fraction between the study and the control group (54.21 ± 88.81% versus 56.01 ± 7.85%, p0.05). The left ventricular mass index (LVMI) in study group was higher than in control group (137.05 ± 9.42 versus 123.57 ± 7.01 g/m(2), p=0.001). The plasma levels of adrenomedullin in study group was higher than in control group (25.97 ± 5.48 versus 18.32 ± 6.97 ng/L, p=0.001). Levels of plasma adrenomedullin were positively correlated with LVMI in the study (r=0.734, p0.05) and control group (r=0.592, p0.05).Anxiety disorders are associated with elevated plasma adrenomedullin levels and increased left ventricular hypertrophy in patients with essential hypertension. The clinical significance of these changes requires further investigation.

Purpose: To evaluate the Integrated Cochlear Profile for Assessing Auditory Nerve-Auditory Pathway Integrity (ICP-API), as proposed by our group, in the selection of cochlear implant candidates. Procedures: The API of the candidates for cochlear implantation were assessed with the ICP-API, which consists of 5 categories including: audiological testing; radiological imaging study; ear-canal electric response audiometry; response to environmental sounds; speech development level. The auditory rehabilitation effects of the cochlear implantation receivers were evaluated postoperatively. Results: Sixty-six of 68 candidates who met the criteria of the ICP-API received cochlear implantation with improved hearing and speech development postoperatively. The remaining 2 of the 68 candidates were diagnosed with bilateral auditory nerves aplasia, and therefore failed cochlear implants were avoided. Conclusion: The ICP-API is valuable and feasible for the selection of cochlear implant candidates. The API should be considered as one of the most important criteria for cochlear implant candidate selection.

Cardiac transplantation is one of the most effective treatments of end stage heart failure to date, although it comes with risks. One of the major complications of cardiac transplantation is allograft failure, which is caused by ischemic injuries, pulmonary hypertension and chronic rejection. Recent animal and human studies have demonstrated that cardiac lymphatic obstruction leads to significant myocardial fibrosis and depression in contractile forces. We hypothesize that lymphatic interruption, which is almost inevitable after cardiac transplantation, is a major cause of cardiac allograft failure through direct damages to the myocardium and also through the formation of allograft coronary vasculopathy.

Aims: To evaluate the safety and efficacy of a new approach for transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty (PBMV). Methods: One hundred and two patients with rheumatic mitral stenosis were randomized into two groups. In the study group (RA approach), an imaginary horizontal line was drawn from the top end of the tricuspid valve under anteroposterior fluoroscopic view. The intersection of the horizontal line and the right edge of the corresponding thoracic vertebra was defined as the upper border of the Fossa ovalis. The atrial septum was punctured from a point 0.5 cm below the upper border of the Fossa ovalis. In the control group (LA approach), an imaginary horizontal line was drawn between the upper and middle third of the left atrium, and the intersection of this horizontal line and the right edge of the corresponding thoracic vertebra was used as an atrial septum puncture point. Results: Atrial septum puncture succeeded in all patients in the study group and in 72.6% of the patients in the control group (p < 0.01). The average fluoroscopy times for transseptal catheterization in the study and the control groups were 2.0 ± 0.5 and 3.0 ± 1.0 min, respectively (p < 0.01). Transseptal catheterization was subsequently achieved using the RA approach in the 14 patients from the control group in whom the LA approach failed. Conclusions: The RA approach is a safe and effective means for transseptal catheterization in patients undergoing PBMV.

To investigate the effect of an anti-fibrotic tetra peptide Ac-SDKP on vascular fibrosis by regulating extracellular regulated protein kinase (ERK1/2) activity through Ang II.Rat vascular adventitial fibroblasts were cultured in vitro. They were randomly divided into control group, Ang II (10(-6) mmol/L) group, Ang II and Ac-SDKP joint action group, PD98059 group. Type I, III collagen contents in adventitia fibroblasts were measured by RT-PCR and the expressions of matrix metalloproteinases (MMP-2) and transforming growth factor-beta1 (TGF-beta1) were determined by Western blot.Ac-SDKP could reduced Ang II-induced expression of type I, III collagen secretion and TGF-beta1 at mRNA,and increase MMP-2 expression, PD98059 could inhibit the above effect.The results suggested that Ac-SDKP could inhibit the formation and development of vascular fibrosis through blocking ERK1/2 pathway mediated by Ang II. Ac-SDKP therefore served as an antifibrotic factor in vascular fibrosis.

The present study was to explore signaling mechanisms underlying nicotine-induced inhibition of large-conductance calcium-activated potassium channels (BK(Ca)).8 week male Wistar rats were divided randomly into saline group and nicotine group and received respectively injection with saline or nicotine (Sigma, Shanghai, China) at 2 mg/(kg x d) for 21 days. Coronary vascular smooth muscle cells were dissociated enzymatically. Dissociated smooth muscle cells were interfered with CPT-cAMP (100 micromol/L) or forskolin (10 micromol/L). The signal channel open dwell-time (To), close dwell-time (Tc) and open probability (Po) were recorded.CPT-cAMP or forskolin significantly prolonged To, shorten Tc and increased Po in saline group (P0.01). But in nicotine group To, Tc and Po did not been changed.This phenomenon may serve as a physiological mechanism that nicotine inhibits BK(Ca) channel activity to increase via cAMP/PKA-dependent pathway.

To investigate the clinical application, feasibility and value of 3 T whole-heart contrast enhanced free-breathing navigator-gated three-dimensional coronary magnetic resonance angiography (CE-CMRA).3 T CE-CMRA was used to examine patients with suspected coronary heart disease (CAD). Gd-BOPTA (0.2 mmol/kg) was injected intravenously with slow infusion rate (0.3 ml/s) to perform enhancement. Data were post-processed to obtain principal branches of coronary artery and picture quality was evaluated. According to results of selective coronary arteriography (SCAG), the diagnostic accuracy of CE-CMRA for diagnosing CAD was judged by means of detecting significant stenosis (50%) of the principal branches based on the 9 segments of coronary artery.Twenty-three out of 26 patients successfully completed the examination. The mean scanning time was (10.4 ± 2.1) minutes, 178 out of 202 (88.1%) SCAG demonstrated segments could be evaluated by CE-CMRA. The imaging quality was superior in proximal and middle segments of coronary artery principal branches than in distal segments. Based on patient-level, there were 9 positive cases and 14 negative cases examined by CE-CMRA compared with 11 positive cases and 12 negative cases examined by SCAG, respectively. The whole diagnose accordance rate of CE-CMRA was 91.3% (21/23) compared with SCAG. The sensitivity, specificity and negative predictive values were 81.8% (9/11), 88.5% (169/191) and 98.8% (9/31) respectively.3 T CE-CMRA is a feasible non-invasive imaging modality for diagnosing CAD, especially to detect significant stenosis in proximal and middle segments of coronary artery principal branches. However, the detecting efficacy is limited in assessing stenosis of distal segment and small branches of coronary artery.

to observe the association between myocardial fibrosis, detected by delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) and arrhythmia in patients with hypertrophic cardiomyopathy (HCM).forty-eight untreated HCM patients who underwent Cine MR, DE-MRI, 24 h ambulatory Holter electrocardiogram and ECG examinations were recruited. Extent of myocardial fibrosis (fibrosis mass/total LV mass) was assessed using DE imaging. Association between arrhythmias including premature ventricular complexes (PVCS ≥ 200), supra-ventricular tachycardia (SVT), non-sustained ventricular tachycardia (NSVT), atrio-ventricular block (AVB) and intra-ventricular block (IVB) detected by Holter monitoring and ECG with regard to delayed enhancement (DE) on contrast enhanced CMR was analyzed.myocardial fibrosis was detected in 35 patients. Incidence of arrhythmia was significantly higher in patients with DE than in patients without DE (P0.05). Extent of myocardial fibrosis was significantly associated with the QRS duration (r = 0.33, P0.001).myocardial fibrosis detected by DE-CMR was associated with arrhythmia in patients with HCM. DE-CMR might be helpful to detect high-risk HCM patients prone to arrhythmia.

To investigate the clinical value of different magnetic resonance (MR) pulse sequences in diagnosis of spinal metastatic tumor.Fifteen patients with clinically suspected spinal metastatic tumor were included in this study. These patients were with documented primary tumors. Four MR pulse sequences, T1-weighted spin echo (T1WI SE), T2-weighted fast spin echo (T2WI FSE), short time inversion recovery (STIR), and gradient echo 2-D multi echo data imaging combination (GE Me-2D) were used to detect spinal metastasis.Fifteen vertebral bodies were entire involvement, 38 vertebral bodies were section involvement, and totally 53 vertebral bodies were involved. There were 19 focal infections in pedicle of vertebral arch, 15 metastases in spinous process and transverse process. Fifty-three vertebral bodies were abnormal in T1 WI SE and GE Me-2D, 35 vertebral bodies were found abnormal in T2WI FSE, and 50 vertebral bodies were found abnormal in STIR. The verges of focal signal of involved vertebral bodies were comparatively clear in T1WI SE, comparatively clear or vague in T2WI FSE, vague in STIR, and clear in GE Me-2D.GE Me-2D may be the most sensitive technique to detect metastases. So three sequences (T1WI SE, T2WI FSE, GE Me-2D) can demonstrate the early changes of spinal metastasis roundly.

To evaluate the usefulness of multi-slice spiral CT (MSCT) in the post-operative assessment of cochlear implanted electrode.Twenty-three cochlear implant recipients were enrolled in this study. All patients were examined with a SOMATOM Sensation 16-slice CT scanner (Siemens) using the following parameters: 120 kV, 100 mAs, 0. 75 mm collimation, 1 mm reconstruction slice thickness and increment, a pitch factor of 1, and a FOV of 100 mm. The axial images of interested ears were reconstructed with 0.1 mm increment and a FOV of 50 mm, and then volume rendering technique (VRT) reconstruction were done on the work station.The electrode arrays were detected on axial CT images. Both inner ear and electrode array could be displayed on one image simultaneously. VRT provided an intuitionistic view of the relationship between electrode array and cochlea VRT showed the number of the electrode array in 20 patients implanted with Combi 40 + standard electrode array and demonstrated the shape, position, and insertion depth. The electrode array number determined by VRT was in accordance with the surgical findings in 18 patients, and was underestimated in two patients. In 3 patients with Combi 40 + compressed electrode array, only 4 to 5 electrodes arrays were clearly identified and others were not observed.MSCT with VRT can provide useful three-dimensional information of the electrode array and indicate the exact relationship between electrode array and cochlea.

To explore the clinical value of magnetic resonance (MR) imaging in the diagnosis of the complications after breast augmentation with polyacrylamide hydrogel injection.MRI was performed in 16 patients who had breast augmentation with polyacrylamide hydrogel injection. The results of magnetic resonance imaging were compared with the clinical symptoms.MRI examinations of the 16 patients showed that (1) 4 breasts in 2 patients were comparatively natural; (2) a large lacteal cyst was detected in one patients in lactation; (3) breast asymmetry occurred in 3 patients (6 sides); (4) in 10 patients (20 sides), the injected gel was in irregular form. The results of MRI were in accord with the clinical symptoms.MRI is of great diagnostic value for the complications after breast augmentation with polyacrylamide hydrogel injection.

A simple strategy for the indirect detection of 3,3',5,5'-tetrabromobisphenol A (TBBPA) was developed with a surface imprinted sensor based on an electrochemical reduced graphene modified carbon electrode. The preparation procedure of imprinted electrode and the response mechanism of the imprinted electrode toward TBBPA are discussed in detail. The electrochemical characteristics of the imprinted sensor were investigated using cyclic voltammetry and their morphologies were characterized using scanning electron microscopy. The indirect detection for TBBPA was successfully implemented by monitoring the peak current of Fe(CN)6(3-/4-)-TBBPA complex. The response currents of the imprinted sensor exhibited a linear relationship toward the TBBPA concentration range from 0.5 to 4.5 nM with a detection limit of 0.23 nM (S/N = 3). The fabricated electrochemical imprinted sensor was successfully applied to the detection of TBBPA in rain and lake water samples using the standard addition method. With the advantages of high sensitivity and simple operation, the determination methodology is a promising candidate for TBBPA detection in real water samples.

Purpose: To investigate the effect of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells (EPCs). Methods: Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation. The cells were stimulated with adrenomedullin, before and after the treatment of adrenomedullin-receptor antagonist, adrenomedullin 22-52, or a PI3K inhibitor LY294002. Results: Adrenomedullin dose-dependently increased the number of EPCs (P < 0.05). Adrenomedullin also significantly decreased apoptosis rate of EPCs in a concentration-dependent manner (P < 0.05). In the isolated human mononuclear cells pretreated with adrenomedullin 22-52 or LY294002, adrenomedullin failed to increase the number of EPCs or to reduce the level of apoptosis. Conclusions: Adrenomedullin increases the number of EPCs and decreases their apoptosis. These actions are likely mediated by PI3K signaling pathways. The clinical importance of these favourable effects on EPCs remains to be determined.

To assess the vascularity of hepatocellular carcinoma (HCC) before and after transcatheter arterial chemoembolization (TACE) with the quantitative parameters obtained by first pass perfusion weighted MR imaging (FP-MRI).Seventeen consecutive patients with one to three lesions in liver underwent FP-MRI before treatment. FP-MRI was also performed one, three, six, nine months, and one year after TACE. The baseline signal intensity (S0) of pre-TACE and one month after TACE was analyzed, the vascularity of HCC assessed by steepest slope of the signal intensity versus time curves (SS) was blindly correlated with their DSA feature and clinical outcome.No significant difference was found on baseline signal intensity (S0) between pre-TACE and one month after TACE (F=0.309, P=0.583), The SS (mean, 32% per second) of lesion one month after TACE was lower than that of pre-TACE (mean, 69% per second), but with no statistical significance (F=3.067, P=0.092). When local recurrence occurred, the time intensity curves became steeper. The vascularity of HCC before and after TACE graded by SS closely correlated with that by DSA (K=0.453, P0.05).FP-MRI is a useful criterion for selecting effective interventional treatment for patients with HCC in their initial treatment and during follow up.

To observe the change of tumor microcirculation after transcatheter arterial chemoembolization (TACE) with bletilla microspheres by using first pass perfusion MR imaging (FP) and Chinese ink casting.VX2 carcinoma cells were surgically implanted into the left and right lobes of liver of 30 New Zealand white rabbits, which were divided into 3 groups at random. Emulsion of lipiodol mixed with mitomycin C, and 5-FU bletilla microspheres were injected into the hepatic artery respectively, and saline was used as control agent. MR imaging was performed with turbo-flash sequence 14 d after tumor implantation and 7 d after interventional therapy. The steepest slopes (SS) of the signal intensity versus time curves were created for quantitative analysis, 7.5% Chinese ink gelatin solution was injected through ascending artery (17 cases) or portal vein (2 cases) for lesion microvessel area (MVA) measurement after the last MRI examination. The correlation between perfusion imaging and MVA was studied blindly.The SS values at the rim of tumor in lipiodol group (mean, 49% per second) and bletilla group (mean, 35% per second) were significantly decreased (P0.05) as compared with control group (mean, 124% per second), no difference was found between lipiodol and bletilla groups (P0.05). In lipiodol group, the MVAs (24 974+/-11 836 microm(2)) in the center of the tumor were significantly smaller than those of the control group (35 510+/-15 675 microm(2)) (P0.05), while the MVAs (80 031+/-22 745 microm(2)) around the tumor were significantly increased because small and dense plexuses appeared around the tumor which correlated to intense reaction of granulation tissue. None of the vessels was seen in the tumor in bletilla group, the peripheral MVAs of the tumor were significantly smaller than those of the control group (P0.05) and lipiodol group (P0.05). There was a good correlation between SS and MVAs in control group (r(s), 0.985, P0.0001) and bletilla group (r(s), 0.743, P0.05), the correlation was not significant in lipiodol group (r(s), 0.527, P0.05).TACE with bletilla microspheres may enhance its anti-tumor effect by inhibiting the angiogenesis, and FP-MRI provides useful information to assess the TACE effect by depicting tumor vascularization and perfusion.

Objectives To reveal the relationship of brain motion and cerebrospinal fluid (CSF) flow by phase-contrast cine MRI, and to evaluate this technique in differentiating between arachnoid cysts and subarachnoid space enlargement. Methods Using a phase-contrast cine MRI pulse sequence, we measured brain motion and CSF flow during the cardiac cycle in 10 healthy volunteers and 10 patients with MRI-suspected arachnoid cyst or subarachnoid space enlargement. CSF stroke volume curve was illustrated according to flow quantification, and time-signal intensity curve was traced. The two curves were compared. Results This study showed that brain motion was due to the volume difference between arterial and venous blood flow during a cardiac cycle, and thus drives CSF pulsation. Arachnoid cysts and subarachnoid space enlargement carried different curve patterns, demonstrating that phase-contrast MRI and flow quantification can be a useful and reliable technique for non-invasive evaluation of brain motion and CSF flow. Conclusion Arachnoid cysts can be successfully differentiated using phase-contrast cine MRI from subarachnoid space enlargement.

BACKGROUND: Endothelial progenitor cells (EPCs) might be useful in the management of coronary artery disease (CAD). OBJECTIVE: The aim of this study was to investigate the effects of xuezhikang, an extract of Chinese red yeast rice, on the proliferation and adhesion capacity of EPCs from the peripheral blood of patients with stable CAD. METHODS: Mononuclear cells from 20 Chinese patients (14 men, 6 women; mean [SD] age, 64.5 [2.8] years [range, 60–69 years]) were isolated using densitygradient centrifugation. After 4 days in culture, the attached cells were treated with different concentrations of xuezhikang (50, 125, 250, and 500 ng/mL; 20 samples/group), atorvastatin (10 ng/mL; n = 20), or phosphate-buffered saline (control, n = 20) for 3 days. Cells that were positive for 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine-labeled acetylated low-density lipoprotein and lectin were defined as EPCs. They were counted by 2 independent investigators in ≥4 randomly selected highpower fields per well. EPCs were then treated and adherent cells were counted by the independent investigators who were blinded to study drug administration. RESULTS: The mean (SD) number of cultured EPCs in the xuezhikang 50-, 125-, 250-, and 500-ng/mL groups (205 [28], 244 [31], 283 [42], and 334 [43] cells, respectively; all, P < 0.001) was significantly increased in a dose-dependent manner compared with the control group (167 [36] cells). The adhesion capacity of the EPCs was significantly greater in the 4 xuezhikang groups (51 [9], 62 [10], 71 [11], and 83 [12] cells; all, P < 0.001) when compared with that of the control group (41 [7] cells). Both the number of EPCs (327 [49] cells) and the number of adhesive EPCs (84 [15] cells) in the atorvastatin group were also significantly increased compared with the control group (both, P < 0.001); however, these increases were not significantly different from those in the xuezhikang 500-ng/mL group. CONCLUSIONS: Xuezhikang was associated with significantly enhanced proliferation and adhesion capacity of EPCs derived from the peripheral blood of these patients with stable CAD. These effects were not significantly different between xuezhikang and atorvastatin.