Clinical and Investigative Medicine最新文献

Purpose: To evaluate the relationship between the serum calcitonin gene-related peptide (CGRP) level and severity of coronary stenosis.

Methods: A total of 233 eligible patients who underwent coronary angiography were divided into two groups: a control and a coronary heart disease (CHD) group. The angiographic severity of coronary stenosis was evaluated by SYNTAX and Gensini scores. The incidence of major adverse cardiovascular events within two years was collected.

Results: A negative correlation between serum CGRP levels and Gensini scores was observed in all patients (r=-0.352, p<0.001), the control group (r=-0.422, p<0.001) and the CHD group (r=-0.393, p<0.001). Serum CGRP levels were negatively associated with SYNTAX scores in the CHD group (r=-0.522, p<0.001). The area under the curve of CGRP for identifying high SYNTAX scores (>22) was 0.772 [95% confidence interval (CI): 0.673-0.870, p<0.001], and for identifying high Gensini scores was 0.744 (95% CI: 0.646-0.842, p<0.001). A CGRP concentration of 25.05 pg/ml was selected as the cutoff point. A low CGRP level (<25.05 pg/ml) was an independent predictor of severe coronary stenosis, a SYNTAX score >22 [odds ratio (OR) =5.819, 95% CI: 2.240-15.116; p<0.001] and a high Gensini score (>64) (OR=4.943, 95% CI: 2.020-12.095; p<0.001). The low CGRP group had a higher incidence of major adverse cardiovascular events within two years (11.1 vs. 3.1%, p=0.031).

Conclusion: In coronary atherosclerosis patients without acute myocardial injury, serum CGRP levels were negatively associated with the severity of coronary stenosis.

Purpose: To evaluate the distribution of the posterior-anterior corneal radius ratio (B/F ratio; posterior corneal radius/anterior corneal radius) in patients without corneal abnormalities, and to investigate which parameters affect this ratio.

Methods: Five thousand eyes from 5,000 patients who underwent cataract surgery were recruited to this study. We explored the linear relationship between B/F ratio and 13 variables using Principal Component-Multivariate Linear Regression Analysis.

Results: The B/F ratio was negatively correlated with the difference between simulated keratometry (SimK) and true net power (TNP), central corneal thickness, spherical aberration (SA), and posterior corneal astigmatism and positively correlated with posterior corneal radius, corneal posterior surface, axial length (AL) and anterior corneal radius. Several variables (central corneal thickness, difference between SimK and TNP and asphericity coefficient (Q-value) of the posterior corneal surface) had the highest loading on the final score. B/F ratio reflects the refractive state and anatomical structure of the cornea: thus, higher B/F ratios were associated with larger posterior corneal surface curvature radius, longer axial length, thinner central corneal thickness, lower high order aberrations of the cornea and SA, and the numerical difference between simK and TNP gradually reduced. In clinical practice, for patients with lower B/F ratio, special care should be taken in the choice of system used for intraocular lens (IOL) measurements.

Purpose: Incidence of contrast induced nephropathy (CIN) and related risk factors in patients with liver cancer and chronic kidney disease after trans-catheter arterial chemoembolization (TACE) is higher. The purpose of this study was to investigate the feasibility and safety of TACE therapy in such patients.

Methods: A retrospective analysis was performed on 103 patients with liver cancer and chronic kidney disease who underwent TACE treatments. TACE was performed according to Seldinger's technique of arterial embolization with minor modifications. Based on CIN diagnostic criteria, patients were divided into non-CIN (n=89) and CIN (n=14) groups. Multiple clinical parameters were assessed for the two groups after TACE. Serum creatinine levels were measured 48-72 h after TACE.

Results: Tumor size (>5 cm), TACE frequency, contrast agent dosage, solitary kidney, volume of iodized oil used in the TACE (ml) and urea levels were significantly higher in CIN group in comparison with the non-CIN group, while serum albumin and haemoglobin levels were significantly lower. Multivariate logistic regression analysis confirmed that the volume of iodized oil and TACE frequency were significantly positively correlated, and serum albumin level was negatively correlated in the CIN group.

Conclusion: Volume of iodized oil, TACE frequency and low serum albumin levels were found to be independent risk factors for CIN after TACE. Thus, it is safe and feasible for hepatocellular carcinoma patients with chronic kidney disease to receive TACE treatment, but adverse events management after TACE needs to be addressed.

Human immunodeficiency virus (HIV) continues to have a profound global health impact. New infections continue at a high rate despite the development of prophylactic therapies, prompting the need for development of novel preventative approaches. Antimicrobial peptides (AMPs), such as LL-37, display broad microbicidal properties and have potential as anti-HIV agents. LL-37 has been studied for its anti-HIV activity and the limited data available suggest it can inhibit HIV infection in primary T cells as well as exert inhibitory effects on key HIV enzymes. Its immunomodulatory properties may both enhance and inhibit HIV replication. In addition, LL-37 has both 1) the ability to kill other sexually-transmitted pathogens and 2) spermicidal activity; thus, it is a good candidate for multipurpose prevention technology. Further investigation of its anti-HIV activity is warranted.

The 2020 Annual General Meeting (AGM) and Young Investigators’ Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherches Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was the first meeting to be hosted virtually. The theme was “Navigating Uncertainty, Embracing Change and Empowering the Next Generation of Clinician-Scientists”, and the meeting featured lectures and workshops that were designed to provide knowledge and skills for professional development of clinician investigator trainees. The opening remarks were given by Jason Berman (President of CSCI/SCRC), Tina Marvasti (President of CITAC/ACCFC) and Nicola Jones (University of Toronto Clinician Investigator Program Symposium Chair). Dr. Michael Strong, President of the Canadian Institutes of Health Research, delivered the keynote presentation titled “CIHR’s COVID-19 Response and Strategic Planning”. Dr. John Bell (University of Ottawa) received the CSCI Distinguished Scientist Award, Dr. Stanley Nattel (Université de Montréal) received the CSCI-RCPSC Henry Friesen Award (RCPSC; Royal College of Physicians and Surgeons of Canada) and Dr. Meghan Azad (University of Manitoba) received the CSCI Joe Doupe Young Investigator Award. Each scientist delivered talks on their award-winning research. The interactive workshops were “Developing Strategies to Maintain Wellness”, “Understanding the Hidden Curriculum: Power and Privilege in Science and Medicine”, “Hiring a Clinician Scientist Trainee: What Leaders Are Looking For” and “COVID-19: A Case Study for Pivoting Your Research”. The AGM included presentations from clinician investigator trainees nationwide. Over 70 abstracts were showcased, most are summarized in this review, and six were selected for oral presentations.

Purpose: This study aimed to identify potential diagnostic and therapeutic biomakers for the development ofbreast cancer (BC).Methods: GSE86374 dataset containing 159 samples was acquired from the Gene Expression Omnibus (GEO) database followed by differentially expressed genes (DEGs) identification and cluster analysis. Corresponding functional enrichment and protein-protein interaction (PPI) network analyses were performed to identify hub genes. Prognostic evaluation using clinical information obtained from TCGA database and hub genes was conducted to screen for crucial indicators for BC progression. The risk model was established and validated.Results: In total, 186 DEGs were identified and grouped into four clusters: 96 in cluster 1; 69 in cluster 2; 16 in cluster 3; and 5 in cluster 4. Functional enrichment analysis showed that DEGs, including ADH1B in cluster 1, were dramatically enriched in the tyrosine and drug metabolism pathways, while genes in cluster 2, including SPP1 and RRM2, played crucial roles in PI3K-Akt and p53 signalling pathway. SPP1 and RRM2 served as hub genes in the PPI network, resulting in an support vector machine classifier with good accuracy and specificity.Ad ditionally, the results of prognostic analysis suggest that age, metastasis stage, SPP1 and ADH1B were correlated with risk of BC, which was validated by using the established risk model analysis.Conclusion: SPP1, RRM2 and ADH1B appear to play vital roles in the development of BC. Age and TNM stage were also preferentially associated with risk of developing BC. Evaluation of the risk model based on larger sample size and further experimental validation are required.

Purpose: To investigate the therapeutic effects of minocycline combined with tinidazole in the treatment of chronic periodontitis (CP).Methods: Seventy-three CP patients treated May 2018–December 2019 at Yuyao People’s Hospital (Yuyao, China) were enrolled in this study: 34 were treated with minocycline alone (control group; CG) and 39 were treated with a combination of minocycline and tinidazole (observation group; OG). Both groups were treated continuously for four weeks and plaque index (PLI), bleeding index (BI), periodontal pocket depth (PD), periodontal attachment level (PAL) and alveolar bone height were compared before and after treatment. Pain was evaluated using the visual analogue scale (VAS). Levels of TNF-α and IL-6 before and after treatment were determined using an enzyme-linked immunosorbent assay. Adverse reactions were compared.Results: In each group, PLI, BI, PD, PAL and alveolar bone height were lower after treatment (P<0.05), and those in OG were lower than those in CG (P<0.05). TNF-α and IL-6 levels in both groups were lower after treatment (P<0.05), and the levels in serum of the OG were lower than those of the CG (P<0.05). After treatment, the VAS in OG was lower than that of CG (P<0.05). There was no significant difference in adverse reactions between groups (P>0.05).Conclusion: Minocycline combined with tinidazole was more effective in treating CP than minocycline alone. This drug combination improved the periodontal indexes and inflammatory reaction of CP and relieved their pain. No significant difference in adverse reactions was seen.

Purpose: Obstructive sleep apnea (OSA) leads to endothelial dysfunction and platelet hyperactivity, which arelinked to increased risk of cardiovascular disease and implicated in the development of aspirin resistance. We hypothesized that aspirin resistance is prevalent among OSA patients and aimed to explore effects of continuous positive airway pressure (CPAP) therapy on aspirin responsiveness.Methods: In Phase 1, prevalence of aspirin resistance was determined cross-sectionally in a group of OSA patients (n=59) on daily low-dose aspirin (81 mg) taken before entering the study, for primary or secondary prevention. In Phase 2, aspirin responsiveness before and after initiation of CPAP therapy was compared and stratified by endothelial function in a cohort of aspirin-naïve patients with newly diagnosed OSA (n=18).Results: In Phase 1, prevalence of aspirin resistance was 17%; most patients (56%) were on CPAP therapy. In Phase 2, initiation of CPAP therapy was associated with significant improvement in endothelial function (p=0.03). The mean pre-CPAP aspirin resistance units (ARU) was 569 (SD=75). In subjects with endothelial dysfunction (44%), the mean decrease after initiation of CPAP therapy was 43 ARU (SD=81, p=0.18). In contrast, subjects with normal endothelial function experienced the mean decrease of 8 ARU (SD=116, p=0.83).Conclusion: Aspirin resistance may be prevalent among OSA patients. After initiation of CPAP therapy, we observed a trend towards improvement in aspirin responsiveness among patients with endothelial dysfunction. The role of endothelial dysfunction and aspirin resistance should be explored in further studies that focus on the effect of CPAP on cardiovascular outcomes.

While the separate roles of physicians and scientists are well defined, the role of a physician scientist is broad and variable. In today’s society, physician scientists are seen as a hybrid between the two fields and they are, therefore, expected to be key to the translation of biomedical research into clinical care. This article offers a narrative review on physician scientists and endeavours to answer whether there is an ongoing need for physician scientists today. The historical role of physician scientists is discussed and compared with physician scientists of the 21st century. Fundamental differences and similarities between the separate roles of physicians and scientists are examined as well as the current state of bench to bedside research. Finally, the ability of 21st century physician scientists to impact their respective medical and scientific fields in comparison to non-physician scientists will be discussed. This paper speculates as to why numbers of physician scientists are dwindling and uses the COVID-19 pandemic as an example of rapid translational research. Ultimately, we suggest that physician scientists are important and may have the most impact on their field by working to connect bedside and bench rather than simply working separately in the bedside and bench. To do this, physician scientists may need to lead clinical research teams composed of individuals from diverse training backgrounds.

Purpose: This study aimed to screen hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC)-related feature ribonucleic acids (RNAs) and to establish a prognostic model.Methods: The transcriptome expression data of HBV-associated HCC were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus database. Differential RNAs between HBV-associated HCC and normal controls were identified by a meta-analysis of TCGA, GSE55092 and GSE121248. Weighted gene co-expression network analysis was performed to identify key RNAs and modules. A prognostic score model was established using TCGA as a training set by Cox regression analysis and was validated in E-TABM-36 dataset. Additionally, independent prognostic clinical factors were screened, and the function of lncRNAs waspredicted through Gene Set Enrichment Analysis.Results: A total of 710 consistent differential RNAs between HBV-associated HCC and normal controls were obtained, including five lncRNAs and 705 mRNAs. An optimized combination of six differential RNAs (DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4) was selected and a prognostic score model was constructed. Kaplan-Meier analysis demonstrated that the prognosis of the high-risk and low-risk groups separated by this model was significantly different in the training set and the validation set. Gene Set Enrichment Analysis showed that the co-expression genes of DSCR4 were significantly correlated with neuroactive ligand receptor interactionpathway.Conclusion: A prognostic model based on DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4 was developed that can accurately predict the prognosis of patients with HBV-associated HCC. These genes, as well as histologic grade, may serve as independent prognostic factors in HBV-associated HCC.