Bibliometric and visualized analysis of applying tumor markers in lung cancer diagnosis from 2000 to 2022.

Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Tumor marker (TM) detection can indicate the existence and growth of a tumor and has therefore been used extensively for diagnosing LC. Here, we conducted a bibliometric analysis to examine TM-related publications for LC diagnosis to illustrate the current state and future trends of this field, as well as to identify additional promising TMs with high sensitivity. Methods: Publications regarding TMs in LC diagnosis were downloaded from the Web of Science Core Collection. CiteSpace was applied to perform a bibliometric analysis of journals, cocitation authors, keywords, and references related to this field. VOSviewer was used to generate concise diagrams about countries, institutions, authors, and keywords. Changes in the TM research frontier were analyzed through citation burst detection. Results: A total of 990 studies were analyzed in this work. The collaboration network analysis revealed that the People's Republic of China, Yonsei University, and Molina R were the most productive country, institution, and scholar, respectively. Additionally, Molina R was the author with the most citations. The National Natural Science Foundation of China was the largest funding source. "Carcinoembryonic antigen (CEA) as tumor marker in lung cancer" was the top reference with the most citations, Lung Cancer was the core journal, and "serum tumor marker" experienced a citation burst over the past 5 years. Conclusion: This bibliometric analysis of TMs in LC diagnosis presents the current trends and frontiers in this field. We summarized the research status of this field and the methods to improve the diagnostic efficacy of traditional serum TMs, as well as provided new directions and ideas for improving the LC clinical detection rate. Priority should be given to the transformation of computer-assisted diagnostic technology for clinical applications. In addition, circulating tumor cells, exosomes, and microRNAs were the current most cutting-edge TMs.

Multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector assay of ginsenosides for quality evaluation of ginseng from diverse Chinese patent medicines.

For quality control of Chinese patent medicines (CPMs) containing the same herbal medicine or different herbal medicines that have similar chemical composition, current ″one standard for one species″ research mode leads to poor universality of the analytical approaches unfavorable to discriminate easily confused species. Herein, we were aimed to elaborate a multiple heart-cutting two-dimensional liquid chromatography/charged aerosol detector (MHC-2DLC/CAD) approach to quantitatively assess ginseng from multiple CPMs. Targeting baseline resolution of 16 ginsenosides (noto-R1/Rg1/Re/Rf/Ra2/Rb1/Rc/Ro/Rb2/Rb3/Rd/Rh1/Rg2/Rg3/Rg3(R)/24(R)-p-F11), experiments were conducted to optimize key parameters and validate its performance. A Poroshell 120 EC-C18 column and an XBridge Shield RP18 column were separately utilized in the first-dimensional (1D) and the second-dimensional (2D) chromatography. Eight consecutive cuttings could achieve good separation of 16 ginsenosides within 85 min. The developed MHC-2DLC/CAD method showed good linearity (R2 > 0.999), repeatability (RSD < 6.73%), stability (RSD < 5.63%), inter- and intra-day precision (RSD < 5.57%), recovery (93.76-111.14%), and the limit of detection (LOD) and limit of quantification (LOQ) varied between 0.45-2.37 ng and 0.96-4.71 ng, respectively. We applied it to the content determination of 16 ginsenosides simultaneously from 28 different ginseng-containing CPMs, which unveiled the ginsenoside content difference among the tested CPMs, and gave useful information to discriminate ginseng in the preparation samples, as well. The MHC-2DLC/CAD approach exhibited advantages of high specificity, good separation ability, and relative high analysis efficiency, which also justified the feasibility of our proposed ″Monomethod Characterization of Structure Analogs″ strategy in quality evaluation of diverse CPMs that contained different ginseng.

A practical strategy enabling more reliable identification of ginsenosides from Panax quinquefolius flower by dimension-enhanced liquid chromatography/mass spectrometry and quantitative structure-retention relationship-based retention behavior prediction.

To accurately identify the metabolites is crucial in a number of research fields, and discovery of new compounds from the natural products can benefit the development of new drugs. However, the preferable phytochemistry or liquid chromatography/mass spectrometry approach is time-/labor-extensive or receives unconvincing identifications. Herein, we presented a strategy, by integrating offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), exclusion list-containing high-definition data-dependent acquisition (HDDDA-EL), and quantitative structure-retention relationship (QSRR) prediction of the retention time (tR), to facilitate the in-depth and more reliable identification of herbal components and thus to discover new compounds more efficiently. Using the saponins in Panax quinquefolius flower (PQF) as a case, high orthogonality (0.79) in separating ginsenosides was enabled by configuring the XBridge Amide and CSH C18 columns. HDDDA-EL could improve the coverage in MS2 acquisition by 2.26 folds compared with HDDDA (2933 VS 1298). Utilizing 106 reference compounds, an accurate QSRR prediction model (R2 = 0.9985 for the training set and R2 = 0.88 for the validation set) was developed based on Gradient Boosting Machine (GBM), by which the predicted tR matching could significantly reduce the isomeric candidates identification for unknown ginsenosides. Isolation and establishment of the structures of two malonylginsenosides by NMR partially verified the practicability of the integral strategy. By these efforts, 421 ginsenosides were identified or tentatively characterized, and 284 thereof were not ever reported from the Panax species. The current strategy is thus powerful in the comprehensive metabolites characterization and rapid discovery of new compounds from the natural products.

Comparative Characterization of the Ginsenosides from Six Panax Herbal Extracts and Their In Vitro Rat Gut Microbial Metabolites by Advanced Liquid Chromatography-Mass Spectrometry Approaches.

Ginseng extracts are extensively used as raw materials for food supplements and herbal medicines. This study aimed to characterize ginsenosides obtained from six Panax plant extracts (Panax ginseng, red ginseng, Panax quinquefolius, Panax notoginseng, Panax japonicus, and Panax japonicus var. major) and compared them with their in vitro metabolic profiles mediated by rat intestinal microbiota. Ultrahigh-performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) with scheduled multiple reaction monitoring (sMRM) quantitation methods were developed to characterize and compare the ginsenoside composition of the different extracts. After in vitro incubation, 248 ginsenosides/metabolites were identified by UHPLC/IM-QTOF-MS in six biotransformed samples. Deglycosylation was determined to be the main metabolic pathway of ginsenosides, and protopanaxadiol-type and oleanolic acid-type saponins were easier to be easily metabolized. Compared with the ginsenosides in plant extracts, those remaining in six biotransformed samples were considerably fewer after biotransformation for 8 h. However, the compositional differences in four subtypes of the ginsenosides among the six Panax plants became more distinct.

The value of serum TRAP1 in diagnosing small cell lung cancer and tumor immunity.

This study set out to investigate the clinical significance of serum tumor necrosis factor receptor-associated protein 1 (TRAP1) in diagnosing small cell lung cancer (SCLC) with different clinical stages, and to compare the diagnostic efficiency with neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Besides, to analyze the role of serum TRAP1 in tumor immunity. A total of 91 patients with SCLC, 99 patients with non-small cell lung cancer (NSCLC), 102 patients with pulmonary nodules (PN), and 75 healthy people were included. The concentrations of serum TRAP1 was detected by enzyme-linked immunosorbent assay (ELISA). NSE, CEA, and CA19-9 were detected by chemiluminescence. The results showed that level of TRAP1 in Group SCLC was lower than other three groups (P < 0.01), whereas NSE in SCLC was significantly higher than the others (P < 0.01), and the levels of CEA and CA19-9 were higher than healthy people and PN patients (P < 0.01). There was a significant difference in TRAP1 levels between patients with limited-stage disease SCLC (LD-SCLC) and extensive-stage disease SCLC (ED-SCLC) (P < 0.0001). The sensitivity and specificity of TRAP1 in diagnosing LD-SCLC were 0.964 and 0.560, respectively, and the area under the curve (AUC) was 0.819. The sensitivity and specificity in diagnosing ED-SCLC were 0.810 and 0.868, respectively, and the AUC was 0.933, which showed high diagnostic value. The AUC of these two groups can be increased to 0.946 and 0.947 in combination of four biomarkers, effectively improving the diagnosis rate of SCLC. Our findings have revealed that serum TRAP1 has high diagnostic value for SCLC and high diagnostic sensitivity for LD-SCLC. It is a potential biomarker for SCLC. Combined detection can effectively improve the diagnosis rate of SCLC. TRAP1 may be secreted into the circulation by mature immune cells and participates in tumor immunity as a carrier of tumor antigens.

Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation.

Irrigation regimes should be chosen to maximize crop yield and water use efficiency. To realize high yield and efficient water use with the appropriate furrow irrigation regime, the effects of two regimes (alternate furrow irrigation and conventional furrow irrigation) and three lower soil moisture limits (60, 70, and 80%) were studied on winter wheat yield and water consumption using a multi-level fuzzy comprehensive evaluation method. The results show that under the two regimes, alternate furrow irrigation and conventional furrow irrigation, when the lower limit of the soil moisture is 70%, the harvest index (0.45 and 0.39, respectively) and crop water productivity of winter wheat (1.86 and 1.90 kg m-3, respectively) are highest. The comprehensive fuzzy evaluation model considers multiple measures, including yield, harvest indices, irrigation volume, total water consumption, and crop water productivity - the index values are highest at the 70% condition, which are 0.3468 and 0.3432, respectively. Therefore, it can be concluded that a moderate water deficit is conducive to saving water resources and improving water use efficiency. In conclusion, a multi-level and multi-factor indices system of furrow irrigation regime was constructed based on ensuring winter wheat production. Conventional furrow irrigation is recommended in areas with sufficient irrigation water, while alternating furrow irrigation, which can reduce the total amount of irrigation required, is suitable for areas with water shortages.

A multi-dimensional liquid chromatography/high-resolution mass spectrometry approach combined with computational data processing for the comprehensive characterization of the multicomponents from Cuscuta chinensis.

Challenges encountered in plant metabolites characterization by liquid chromatography/mass spectrometry can arise from the insufficient chromatography separation, the lack of specific database, and low reliability of identification because of the ubiquitous isomerism. Herein, we present an integral approach, by combining comprehensive off-line two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), automatic peak annotation, molecular networking, and collision cross section (CCS) prediction, aimed to improve the resolution and reliability in MS-oriented metabolites characterization. Using the seeds of Cuscuta chinensis as a case, the configuration of an XBridge Amide column of hydrophilic interaction chromatography (HILIC) and a Zorbax SB-Aq column of reversed-phase chromatography (RPC), in an off-line mode, showed the orthogonality of 0.73 and effective peak capacity of 4361. Data-independent high-definition MSE (HDMSE) in the negative mode could enable high-coverage MS2 data acquisition and enhance the ions resolution, while computational peak annotation workflows facilitated by UNIFITM and Global Natural Products Social Molecular Network (GNPS) could efficiently characterize the targeted and untargeted compound analogs. A total of 302 compounds were identified or tentatively characterized, and 109 thereof were unreported. Moreover, CCS prediction (www.allccs.zhulab.cn) provided more possibilities to distinguish 12 pairs of isomers in the lack of reference standards. The 2D-LC/IM-QTOF-MS approach enabled the collection of five dimension of data related to each component (tR by HILIC and RPC, CCS, m/z in MS1 and MS2), and the intelligent metabolites characterization with more reliable MS data. Conclusively, the established integral strategy can be utilized in metabolome analysis to support the quality control of herbal medicines.

Single-incision robotic cholecystectomy versus single-incision laparoscopic cholecystectomy: A systematic review and meta-analysis.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is the result of the ongoing trend to minimally invasive of laparoscopy, but some surgeons thought that the SILC can increase the risk of bile duct injure or bile spillage, and the single-incision robotic cholecystectomy (SIRC) can overcome the drawbacks of SILC. Some articles described that the SIRC had longer operative time and more cost than SILC. The advantages and disadvantages of SIRC have still not been extensively studied. We aimed to investigate the outcomes of SIRC compared to SILC and evaluate the safety and feasibility of SIRC. METHODS: To find relevant studies, the electronic databases PubMed, MEDLINE, The Cochrane Library, and EMBASE were searched to seek information in English literature from 2011 to 2017. Studies comparing SIRC to SILC, for any indication, were included in the analysis. This systematic review and meta-analysis were performed with RevMan Version 5.3. RESULTS: Six comparative studies (n = 633 patients) were included in our analysis. The data showed that the SIRC and SILC had equivalent outcomes for operative time [mean difference (MD) = 17.32, 95% confidence interval (CI): -8.93-43.57, P = .20], intraoperative complications [odd ratio (OR) = 0.48, 95% CI: 0.17-1.39, P = .18], postoperative complications (OR = 0.62, 95% CI: 0.21-1.86, P = .39), hospital stay (MD = -0.01, 95% CI: -0.21-0.19, P = .90), readmissions rate (OR = 0.70, 95% CI: 0.09-5.63, P = .74), and conversion rate (OR = 0.52, 95% CI: 0.14-1.96, P = .33), but total cost was statistically significant (MD = 3.7, 95% CI: 3.61-3.79, P < .00001). CONCLUSION: SIRC is a safe and feasible procedure for cholecystectomy, and the operative time is same as SILC, but the total cost of SIRC is significantly higher than SILC.

Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells.

Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs) can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs), which can be used as a therapeutic approach against type 1 diabetes (T1D). As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2) promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI). Functionally, bmMSCs were reprogrammed into IPCs via COUP-TFI suppression and MafA overexpression. The differentiated cells expressed higher levels of genes specific for islet endocrine cells, and they released C-peptide and insulin in response to glucose stimulation. Transplantation of IPCs into streptozotocin-induced diabetic mice caused a reduction in hyperglycemia. Mechanistically, COUP-TFI bound to the DR1 (direct repeats with 1 spacer) element in the Ins2 promoter, thereby negatively regulating promoter activity. Taken together, the data provide a novel mechanism by which COUP-TFI acts as a negative regulator in the Ins2 promoter. The differentiation of bmMSCs into IPCs could be improved by knockdown of COUP-TFI, which may provide a novel stem cell-based therapy for T1D.

[Landscape ecological risk assessment and its spatio-temporal variations in Ebinur Lake region of inland arid area].

The typical region of the Ebinur Lake Basin was chosen as study area. Landsat TM/OLI images for 1998, 2011 and 2013 were obtained. In the study area, landscape was classified into six types, including cropland, woodland, grassland, water body, bare lake bed, salinized land and unutilized land. Landscape indices and ecological risk index were calculated and spatially interpolated for the whole region, which was divided into five different risk zones: extremely low, low, moderate, high and extremely high ecological risk. They were carried out for assessing the spatio-temporal changes in ecological risk for each landscape pattern. The results showed that the regional landscape patterns had experienced significant changes, and the increase in the area of croplands was the main trend in landscape evolution from 1998-2013. The main part of the regional ecosystem faced extremely high risk in 1998, high risk in 2011 and low risk in 2013. The ecological risk level of the study area was significantly decreased in the overall period, and the total area of change from high to low risk was much greater than those from low to high risk.

Is radiofrequency ablation equal to surgical re-resection for recurrent hepatocellular carcinoma meeting the Milan criteria? A meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of radiofrequency ablation (RFA) with surgical re-resection (SRR) in patients with postoperative recurrent hepatocellular carcinoma (RHCC) meeting the Milan criteria. METHODS: A literature search was performed to identify comparative studies addressing outcomes of both RFA and SRR for RHCC meeting the Milan criteria. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or the random effects model. RESULTS: Five nonrandomized controlled trials were included in the analysis. These studies included a total of 543 patients: 243 treated with RFA and 300 treated with SRR. The SRR group had a better 3-year recurrence-free survival rate compared with RFA group (OR 0.44, 95%CI 0.25-0.77, p=0.004). However, there were no obvious differences between RFA and SRR group in overall survival (OS) rates, re-recurrence rate and OS rates with tumors ≤ 3cm. What's more, the RFA group had a safety advantage with less complications of Clavien classification grade II or higher compared with SRR group (OR 0.21, 95%CI 0.05-0.94, p=0.04). CONCLUSIONS: RFA seemed to be superior to SRR in the treatment of patients with RHCC meeting the Milan criteria on account of clinical safety. However, these findings have to be carefully interpreted due to the lower level of evidence.

Green tea consumption and risk of esophageal cancer: a meta-analysis of published epidemiological studies.

We performed a meta-analysis to analyze the association of various levels of green tea consumption with risk of esophageal cancer. We searched MEDLINE, EMBASE, and the Cochrane Library for studies of green tea consumption and esophageal cancer and identified 12 observational studies. For esophageal cancer, the pooled relative risk (RR) was 1.09 [95% confidence interval (CI), 0.76-1.55] for greatest vs. non/least green tea consumption; however, there was significant heterogeneity across studies (P = 0.00, I(2) = 75.5%). Compared with subjects who drank no/least green tea, the pooled RR was 1.14 (95% CI = 0.97-1.35) for moderate drinkers, 0.94 (95% CI = 0.77-1.13) for those who drank little, and 0.97 (95% CI = 0.77-1.22) for all subjects who had ever drunk green tea. Subgroup analysis showed that the RR was 0.46 (95% CI = 0.29-0.73) for female subjects. The results of the present meta-analysis are that any association between green tea and risk of esophageal cancer remains unclear. Subgroup analyses indicated that greater consumption of green tea might reduce the risk of esophageal cancer in female subjects. However, the results are based on limited research. Further research is needed to confirm the results and clarify the likely biological mechanisms.

Consumption of coffee associated with reduced risk of liver cancer: a meta-analysis.

BACKGROUND: Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case-control and cohort studies to investigate the association between coffee consumption and liver cancer. METHODS: We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case-control studies and seven cohort studies. RESULTS: The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42-0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40-0.63) for case-control studies and 0.48 (95% CI: 0.38-0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25-0.56) in males and 0.60 (95% CI: 0.33-1.10) in females. The OR was 0.45 (95% CI: 0.36-0.56) in Asian studies and 0.57 (95% CI: 0.44-0.75) in European studies. The OR was 0.39 (95% CI: 0.28-0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46-0.66) after adjustment for a history of liver disease. CONCLUSIONS: The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.

Remission induction and maintenance effect of probiotics on ulcerative colitis: a meta-analysis.

AIM: To evaluate the induction of remission and maintenance effects of probiotics for ulcerative colitis. METHODS: Information was retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The induction of remission and promotion of maintenance were compared between probiotics treatment and non-probiotics treatment in ulcerative colitis. RESULTS: Thirteen randomized controlled studies met the selection criteria. Seven studies evaluated the remission rate, and eight studies estimated the recurrence rate; two studies evaluated both remission and recurrence rates. Compared with the non-probiotics group, the remission rate for ulcerative colitis patients who received probiotics was 1.35 (95% CI: 0.98-1.85). Compared with the placebo group, the remission rate of ulcerative colitis who received probiotics was 2.00 (95% CI: 1.35-2.96). During the course of treatment, in patients who received probiotics for less than 12 mo compared with the group treated by non-probiotics, the remission rate of ulcerative colitis was 1.36 (95% CI: 1.07-1.73). Compared with the non-probiotics group, the recurrence rate of ulcerative colitis patients who received probiotics was 0.69 (95% CI: 2.47-1.01). In the mild to moderate group who received probiotics, compared to the group who did not receive probiotics, the recurrence rate was 0.25 (95% CI: 0.12-0.51). The group who received Bifidobacterium bifidum treatment had a recurrence rate of 0.25 (95% CI: 0.12-0.50) compared with the non-probiotics group. CONCLUSION: Probiotic treatment was more effective than placebo in maintaining remission in ulcerative colitis.

Localization of small sized insulinoma by means of combining arteriography with CT: a case report and review of the literature.

BACKGROUND: The majority of pancreatic insulinomas are of small size and conventional imaging examinations such as percutaneous ultrasonography (US), Computerized Tomography (CT) and MRI usually fail to reveal the lesion. In this article we describe the potential role of combining arteriography with CT, which is superior to single arteriography or CT. METHODOLOGY: A 45-year-old man who suffered from significant catecholaminergic and neuroglycopenic symptoms, such as hypodynamia, sweating, impaired memory and confusion, was diagnosed with insulinoma by biochemical tests. The serum level of glucose of fast in the morning was as low as 1.2 mmol/L, coincident with the low serum level of glucose; the serum level of insulin was 28.77 mIU/L. The fasting insulin-to-glucose ratio was higher than 0.4. The C-peptide of 1097.62 pmol/L was higher than normal. The lesion was not identified on US, CT scan or arteriography. However the combination of arteriography with CT revealed the small insulinoma located at junction of the body and the tail of the pancreas, about 1.0 x 0.8 cm. RESULTS: Intraoperative ultrasound (IOUS) verified the lesion which located in the posterior and superior aspect of the pancreas and spleen-preserving distal pancreatectomy was performed. Histopathology confirmed the diagnosis. After the surgery the patient underwent a good recovery and was discharged two weeks later. He has developed no further episodes of hypoglycemia two years after the surgery. CONCLUSION: Combining arteriography with CT is a valuable examination for insulinoma, and IOUS is helpful to verify the lesion. Entire excision of the lesion is the best way of treatment.

A third-generation, long-acting, dihydropyridine calcium antagonist, azelnidipine, attenuates stent-associated neointimal formation in non-human primates.

BACKGROUND: Calcium antagonists have been shown to reduce atherogenesis and improve clinical outcomes in atherosclerotic vascular disease. No study has so far, however, addressed the effects of calcium antagonists on stent-associated neointimal formation. We therefore investigated whether a third-generation calcium antagonist, azelnidipine, attenuates in-stent neointimal formation in non-human primates. METHOD: Male cynomolgus monkeys were fed a high cholesterol diet for 4 weeks, and were randomly assigned to three groups: a vehicle group and two other groups treated with azelnidipine at 3 and 10 mg/kg per day for an additional 24 weeks (n = 12 each). Multi-link stents were then implanted in the iliac artery. RESULTS: Azelnidipine at the high dose reduced neointimal thickness (0.25 +/- 0.02 versus 0.19 +/- 0.02 mm; P < 0.05). Azelnidipine also reduced local oxidative stress and monocyte chemoattractant protein 1 (MCP-1) expression. No difference was found between the three groups in the degrees of injury score, inflammation score, plaque neovascularization, or plasma lipid levels. Azelnidipine also reduced MCP-1-induced proliferation/migration of vascular smooth muscle cells in vitro. CONCLUSIONS: This study demonstrated for the first time that azelnidipine attenuates in-stent neointimal formation associated with the reduced expression of MCP-1 and smooth muscle proliferation/migration in the neointima. These data in non-human primates suggest potential clinical benefits of azelnidipine as a 'vasculoprotective calcium antagonist' in patients undergoing vascular interventions.