Advances in Clinical and Experimental Medicine最新文献

Background: Total cholesterol (TC) levels represent the comprehensive level of human cholesterol metabolism, which is closely related to the nutritional status, metabolic level, disease development, and aging of the human body. Total cholesterol plays an important role in the maintenance of bodily functions, regulation of sexual function, immune regulation, and in the development of organisms. Abnormal TC levels are an important risk factor for cardiovascular disease (CVD), and TC is closely related to the development of many diseases, and is used as an important indicator of human blood lipid levels and overall health status. However, the relationship between serum TC levels and the prognosis of patients with hip fractures remains unclear.

Objectives: To evaluate the association between TC levels and all-cause mortality in patients with geriatric hip fractures.

Material and methods: Elderly patients with hip fractures were screened between January 2015 and September 2019. Patient demographic and clinical characteristics were recorded. Linear multivariate Cox regression models were used to identify the association between TC levels and all-cause mortality. Analyses were performed using Empower Stats and R software.

Results: Three hundred and thirty-nine patients were enrolled. The mean follow-up period was 34.18 months. There were 99 (29.20%) cases of all-cause mortality. Total cholesterol levels after hip fracture were linearly associated with all-cause mortality in the elderly. Linear multivariate Cox regression models showed that TC levels were associated with mortality (hazard ratio (HR) = 0.67; 95% confidence interval (95% CI): 0.53-0.85; p = 0.001 after adjusting for confounding factors). Each 1 mmol/L increase in TC levels was associated with a 33% reduction in morbidity and mortality. Compared with the low-TC group, mortality was significantly lower in the middle-TC group (HR = 0.58; 95% CI: 0.35-0.94; p = 0.027) and high-TC group (HR = 0.45; 95% CI: 0.27-0.75; p = 0.002).

Conclusions: Total cholesterol levels were associated with mortality in geriatric hip fracture patients and could be considered a protective factor for all-cause mortality.

Background: Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes have been reported to be effective in the treatment of cancer. The miR-214-3p is a suppressor miRNA that has been extensively studied and has been proposed as a diagnostic and prognostic biomarker in some cancers.

Objectives: The aim of this study was to investigate whether the regulatory mechanism of hucMSC-derived exosomal miR-214-3p with GLUT1 and ACLY affects the proliferation and apoptosis of gallbladder cancer (GBC) cells.

Material and methods: We found that the target genes of miR-214-3p on the TargetScan website contain GLUT1 and ACLY, and the targeting relationship was verified using luciferases. The GBC-SD cells overexpressing GLUT1 and ACLY were constructed to determine proliferation, apoptosis, migration, and other cellular activities.

Results: We identified hucMSCs and exosomes, and found that the exosomes contained miR-214-3p. Furthermore, TargetScan predicted that miR-214-3p had base interactions with ACLY. Dual luciferase assays showed that miR-214-3p could inhibit ACLY (p < 0.05). The results of quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot showed that exosomal miR-214-3p could inhibit the expression of ACLY and GLUT1 (p < 0.05). Exosomal miR-214-3p can inhibit the proliferation, cloning and migration of GBC-SD cells (p < 0.05). The apoptosis of GBC-SD cells was increased (p < 0.05). The GBC-SD cells overexpressing ACLY and GLUT1 could reverse the efficacy of miR-214-3p.

Conclusions: Exosomal miR-214-3p can inhibit the downstream expression of ACLY and GLUT1. The ACLY and GLUT1 could affect the proliferation and apoptosis of GBC-SD cells.

Background: Recent studies have revealed the usefulness of synovial calprotectin (CLP) in diagnosing chronic periprosthetic joint infections (PJIs). However, there is still a lack of evidence to support the use of serum CLP in the diagnosis of early PJIs and surgical site infections (SSIs) after total joint arthroplasties (TJAs).

Objectives: The primary aim of this study is to investigate the standard kinetics of CLP concentrations in the blood during the very early postoperative period after non-complicated total hip arthroplasty (THA) and total knee arthroplasty (TKA). The secondary aim was to perform a preliminary comparison of CLP concentrations between non-infected patients and patients with recognized SSIs.

Material and methods: A total of 64 consecutive patients who underwent primary THA and TKA were included in this prospective research. Sixty patients (30 THA and 30 TKA) were scheduled to determine the standard shape of the blood CLP curve and the expected concentrations during the first 5 postoperative days after non-complicated TJAs. In 4 additonal patients, early SSI was confirmed, and they were included in a separate SSI subgroup.

Results: Calprotectin demonstrated a linear increase during the first 5 postoperative days. Statistically significant differences in CLP concentrations between non-infected cases and SSIs were not observed. The preoperative median results with interquartile range (Q1-Q3) were 0.52 (0.39-0.64) mg/dL and 0.5 (0.47-0.52) mg/dL (p = 0.77), while post operation they were as follows: on postoperative day 1: 0.88 (0.53-1.3) mg/dL and 0.86 (0.62-1.1) mg/dL (p = 0.84), on postoperative day 3: 1.77 (1.29-2.08) mg/dL and 1.85 (1.70-1.95) mg/dL (p = 0.72), and on postoperative day 5: 2.32 (1.79-2.67) mg/dL and 2.56 (2.25-2.83) mg/dL (p = 0.55), respectively.

Conclusion: Serial CLP measurements during the early postoperative period revealed a linear (statistically significant) increase in concentration to postoperative day 5 without an evident point of decrease. A significant difference in median values and the course of curve patterns between the non-complicated and SSI groups was not observed.

Background: Iron is a vital element for the growth of bacteria. Bacteria use several strategies to scavenge iron, such as siderophores, which are thought to be important virulence components. The mammalian host uses various iron-binding substances to make iron unavailable for bacterial uptake. Deferoxamine (DFO) is a semi-synthetic iron chelator that has been licensed for medical use. Iron chelators like DFO may provide an alternative therapeutic technique for treating Gram-negative bacteria infections, which frequently display multidrug resistance.

Objectives: We assumed that iron deprivation or interactions with the cell membrane caused by DFO or increased siderophore synthesis may cause the inhibition or inactivation of proteins and enzymes necessary for critical processes in bacteria. Additionally, we proposed that these bacterial alterations might be the origin of synergistic interactions between DFO and several antibiotics.

Material and methods: To test this hypothesis, we used disc diffusion, broth microdilution and checkerboard synergy testing methods on combinations of DFO with ceftriaxone, cefepime, meropenem, amikacin, levofloxacin, and tigecycline, respectively, in a total of 55 isolates (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Proteus mirabilis strains - 11 isolates for each genus).

Results: No synergistic or antagonistic interactions were observed between DFO and the tested antibiotics in the E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii isolates, while the addition of DFO significantly increased the inhibition zone diameters of cefepime, amikacin, meropenem, tigecycline, and levofloxacin in P. mirabilis isolates. According to the checkerboard synergy results, a synergistic interaction was found between DFO and tigecycline, cefepime and amikacin for P. mirabilis isolates.

Conclusions: Among the investigated bacteria, a synergy between antibiotics and DFO was only discovered against P. mirabilis. We do not believe that this entirely disproves our hypothesis, though. The production of siderophores triggered by the increased metabolic activity of actively proliferating bacteria at the infection site may provide better results. Therefore, expanding these investigations and developing infection models through animal testing would be advantageous.

Background: Skeletal anchorage has been the subject of study for many years. Recently, orthodontic mini-implants (MIs) were described as effective tools for anchorage and were named temporary anchorage devices (TADs). The success of MIs depends on their primary stability, which is defined as the lack of mobility in the bone after implant insertion, and the relevant factors affecting primary stability.

Objectives: This study aimed to compare the primary stability of used self-drilling (SD) and self-tapping (ST) MIs with unused ones by performing the insertion torque measurement, Periotest and pull-out test.

Material and methods: Forty-six used (23 ST, 23 SD) and 46 unused (23 ST, 23 SD) MIs (1.5 mm × 8 mm) were inserted into a synthetic bone with the use of a digital screwdriver. Maximum insertion torque (MIT) values were recorded during the placement of MIs, and then Periotest measurements were made. Following the MIT and Periotest measurements, pull-out tests were performed on all MIs.

Results: The median MIT values (Ncm) of the MIs were as follows: used ST: 17.3, unused ST: 18.9, used SD: 24.1, unused SD: 25.2. The median values obtained after the Periotest were (±): used ST: 0, unused ST: -1, used SD: -3, unused SD: -3. Median pull-out values (N) were: used ST: 148.12, unused ST: 168.12, used SD: 173.12, unused SD: 203.20. Statistically, MIT and pull-out values of the used ST and SD implants were significantly lower compared to those of the unused ST and SD implants (p < 0.05).

Conclusions: Used orthodontic MIs showed poor performance compared with unused implants when they were inserted again in the in vitro conditions.

Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.

Background: Osteosarcoma is a pleomorphic cancer that frequently affects children and teenagers. Although several chemotherapy regimens have been utilized for many years, the best therapeutic option for the treatment of osteosarcoma has not yet been determined.

Objectives: This meta-analysis was designed to assess the clinical efficacy of a high-dose methotrexate, doxorubicin and cisplatin (MAP) regimen and compare its survival outcomes with those of other chemotherapy strategies in patients diagnosed with osteosarcoma.

Material and methods: We systematically searched databases, namely Embase, the Cochrane Library and PubMed, up to August 2022, for relevant studies investigating the impact of the MAP chemotherapy protocol on survival among patients with osteosarcoma. The odds ratio (OR) pooled estimates and their 95% confidence intervals (95% CIs) were calculated.

Results: Twelve studies including 4102 patients were eligible for analysis in this study. The estimated pooled ORs of the 3-year overall survival (OS) and event-free survival (EFS) were OR = 1.08 (95% CI: 0.72-1.62, p = 0.70) and OR = 1.04 (95% CI: 0.81-1.32, p = 0.78, respectively). The 5-year OS and EFS were OR = 0.87 (95% CI: 0.62-1.23, p = 0.42) and OR = 1.13 (95% CI: 0.76-1.68, p = 0.54), respectively, with no statistical differences. The subgroup analysis of MAP compared to a 2-drug regimen (doxorubicin and cisplatin) revealed a significant difference between the 2 chemotherapy strategy groups in 3-year OS rates (OR = 0.72 (95% CI: 0.56-0.92, p = 0.009)) and 5-year EFS rates (OR = 0.57 (95% CI: 0.43-0.76, p < 0.001)).

Conclusion: The MAP chemotherapy strategy for osteosarcoma showed superiority over other regimens, especially over the 2-drug regimen (doxorubicin/cisplatin), in terms of better prognosis and safety.

Background: Prostate cancer (PC) prevention is effectively achieved through its inhibition. Oridonin (ORD), an active diterpenoid isolated from Rabdosia rubescens, has been shown to have an inhibitory effect on PC cells, although its impact on PC is unknown.

Objectives: The present work investigated the actions and probable mechanisms of ORD on cellular proliferation, apoptosis, PC, and the wingless-type MMTV integration site family member 2 (Wnt)/β-catenin signaling pathway using the androgen-independent PC-3 cell line.

Material and methods: In this study, cell viability was analyzed with MTT assay method, apoptotic morphology determined using DAPI dye method, while protein (CD1333, OCT-4, Nanog, SOX-2 & Aldh1A1) and mRNA expressions were analyzed with western blotting and real time polymerase chain reaction (PCR).

Results: We demonstrated a concentration-dependent ORD inhibition of PC-3 cell proliferation and inhibition of induction apoptosis. Furthermore, ORD decreased PC-3 Wnt-2, phosphorylated glycogen synthase kinase-3 (p-GSK3), and β-catenin protein levels and downregulated cyclin-D1 and c-myc messenger ribonucleic acid (mRNA).

Conclusions: Oridonin inhibited proliferation and induced apoptosis in PC-3 cells, with the findings suggesting that it acted via the Wnt/β-catenin pathway to exert its effects. This study demonstrates that ORD may impact PC.

The advent of structural magnetic resonance imaging (sMRI) at the end of the 20th century opened the way toward a deeper understanding of the neurophysiology of psychiatric disorders, substantiating regional structural abnormalities underlying this group of clinical conditions. However, despite abundant and flourishing scientific research, sMRI methodologies are not currently integrated into daily diagnostic practice. One reason behind this failed translation may be the prevailing approach to logical reasoning in neuroimaging: The forward inference via frequentist-based statistics. This reasoning prevents clinicians from obtaining information about the selectivity of results, which are therefore of limited use regarding the definition of biomarkers and refinement of diagnostic processes. Recently, another type of inferential approach has started to emerge in the neuroimaging field: The reverse inference via Bayesian statistics. Here, we introduce the key concepts of this approach, with a particular emphasis on the clinical sMRI environment. We survey recent findings showing significant potential for clinical translation. Clinical opportunities and challenges for developing reverse inference-based neural markers for psychiatry are also discussed. We propose that a systematic sharing of imaging data across the human brain mapping community is an essential first step toward a paradigmatic clinical shift. We conclude that a defined synergy between forward-based and reverse-based sMRI research can illuminate current discussions on diagnostic brain markers, offering clarity on key issues and fostering new tailored diagnostic avenues.

Background: Renal steatosis is an abnormal accumulation of fat in the kidney and may cause chronic kidney disease (CKD) or CKD progression.

Objectives: This pilot study aimed to evaluate the quantitative measurability of the parenchymal distribution of lipid deposition in the renal cortex and medulla using chemical shift magnetic resonance imaging (MRI) and investigate its relationship with clinical stages in CKD patients.

Material and methods: The study groups included CKD patients with diabetes (CKD-d) (n = 42), CKD patients without diabetes (CKD-nd) (n = 31) and control subjects (n = 15), all of whom underwent a 1.5T MRI of the abdomen using the Dixon two-point method. The fat fraction (FF) values in the renal cortex and medulla were calculated from measurements made on Dixon sequences, and then compared between the groups.

Results: The cortical FF value was higher than the medullary FF value in control (0.057 (0.053-0.064) compared to 0.045 (0.039-0.052)), CKD-nd (0.066 (0.059-0.071) compared to 0.063 (0.054-0.071)), and CKD-d (0.081 (0.071-0.091) compared to 0.069 (0.061-0.077)) groups (all p < 0.001). The CKD-d group cortical FF values were higher than those of the CKD-nd group (p < 0.001). The FF values began increasing at CKD stages 2 and 3, and reached statistical significance at stages 4 and 5 in CKD patients (p < 0.001).

Conclusions: Renal parenchymal lipid deposition can be quantified separately in the cortex and medulla using chemical shift MRI. Fat accumulation occurred in cortical and medullary parenchyma in CKD patients, though predominantly in the cortex. This accumulation increased proportionally with the disease stage.