Advances in medical sciences最新文献

Purpose

The aim of this study was to build and validate modified score to be used in the healthcare cost and utilization project databases for further classification of acute pancreatitis (AP).

Materials and methods

The National Inpatient Sample database for the years 2016-2019 was queried for all primary adult discharge diagnoses of AP. An mBISAP score system was created utilizing the ICD-10CM codes for pleural effusion, encephalopathy, acute kidney injury, systemic inflammatory response, and age >60. Each was assigned a 1-point score. A multivariable regression analysis was built to test for mortality. Sensitivity and specificity analyses were performed for mortality.

Results

A total of 1,160,869 primary discharges for AP were identified between 2016 and 2019. The pooled mortality rate was: 0.1%, 0.5%, 2.9%, 12.7%, 30.9% and 17.8% (P ​< ​0.01), respectively for scores 0 to 5. Multivariable regression analysis showed increasing odds of mortality with each one-point increment: mBISAP score of 1 (adjusted odds ratio [aOR] 6.67; 95% confidence interval [CI] 4.69-9.48), score of 2 (aOR 37.87; 95% CI 26.05- 55.03), score of 3 (aOR 189.38; 95% CI 127.47-281.38), score of 4 (aOR 535.38; 95% CI 331.74-864.02), score of 5 (aOR 184.38; 95% CI 53.91-630.60). Using a cut-off of ≥3, sensitivity and specificity analyses reported 27.0% and 97.7%, respectively, with an area under the curve (AUC) of 0.811.

Conclusion

In this 4-year retrospective study of a US representative database, an mBISAP score was constructed showing increasing odds of mortality with each 1-point increase and a specificity of 97.7% for a cut-off of ≥3.

Purpose

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the presence of BCR-ABL protein. Imatinib (IMA) is considered as the first line therapy in management of CML which particularly targets the BCR-ABL tyrosine kinase protein. However, emergence of resistance to IMA hinders its clinical efficiency. Hence, identifying novel targets for therapeutic approaches in CML treatment is of great importance. Here, we characterize a new subpopulation of highly adherent IMA-resistant CML cells that express stemness and adhesion markers compared to naive counterparts.

Materials and methods

We performed several experimental assays including FISH, flow cytometry, and gene expression assays. Additionally, bioinformatics analysis was performed by normalized web-available microarray data (GSE120932) to revalidate and introduce probable biomarkers. Protein-protein interactions (PPI) network was analyzed by the STRING database employing Cytoscape v3.8.2.

Results

Our findings demonstrated that constant exposure to 5 ​μM IMA led to development of the adherent phenotype (K562R-adh). FISH and BCR-ABL expression analysis indicated that K562R-adh cells were derived from the original cells (K562R). In order to determine the role of various genes involved in epithelial–mesenchymal transition (EMT) and stem cell characterization, up/down-regulation of various genes including cancer stem cell (CSC), adhesion and cell surface markers and integrins were observed which was similar to the findings of the GSE120932 dataset.

Conclusion

Treating CML patients with tyrosine kinase inhibitors (TKIs) as well as targeting adhesion molecules deemed to be effective approaches in prevention of IMA resistance emergence which in turn may provide promising effects in the clinical management of CML patients.

Purpose

Chronic pancreatitis (CP) is associated with serious complications and reduced quality of life. Kidney failure is a frequent complication of acute pancreatitis (AP), however limited information is available regarding the impact of CP on this condition. In the kidney, 9 aquaporins (AQPs) are expressed to maintain body water homeostasis and concentrate urine. The purpose of this study was to morphologically assess and analyze the location and expression of AQP2, AQP3 and AQP4 and determine whether CP affects renal structure and expression of AQPs in collecting duct (CD) principal cells.

Materials/methods

CP was induced in domestic pigs through intramuscular injections of cerulein (1 ​μg/kg ​bw/day for 6 days; n ​= ​5); pigs without CP (n ​= ​5) were used as a control group. Kidney samples were collected 6 weeks after the last injection and subjected to histological examination. Expression of AQPs was determined by immunohistochemistry and Western blot.

Results

The kidneys of animals with CP exhibited moderate changes, including glomerular enlargement, increased collagen percentage, numerous stromal erythrorrhages and inflammatory infiltrations compared to control group. Although the total abundance of AQP2 in the CD decreased in pigs after cerulein administration, the difference was not statistically significant. Expression of AQP3 and AQP4 was limited to the basolateral membrane of the CD cells. AQP4 abundance remained relatively stable in both groups, while AQP3 expression increased nearly three-fold in pigs with CP.

Conclusion

This study identified morphological alterations and a statistically significant increase in the expression of renal AQP3 when pigs developed CP.

Purpose

The possible effects of ramelteon, a melatonin receptor agonist on bleomycin-induced lung fibrosis were analyzed via transforming growth factor β1 (TGF-β1), the high mobility group box 1 (HMGB1) and Nod-like receptor pyrin domain-containing 3 (NLRP3) which are related to the fibrosis process.

Materials and methods

Bleomycin (0.1 ​mL of 5 ​mg/kg) was administered by intratracheal instillation to induce pulmonary fibrosis (PF). Starting 24 ​h after bleomycin administration, a single dose of ramelteon was administered by oral gavage to the healthy groups, i.e. PF ​+ ​RM2 (pulmonary fibrosis model with bleomycin ​+ ​ramelteon at 2 ​mg/kg) and PF ​+ ​RM4 (pulmonary fibrosis model with bleomycin ​+ ​ramelteon at 4 ​mg/kg) at 2 and 4 ​mg/kg doses, respectively. Real-time polymerase chain reaction (real-time PCR) analyses, histopathological, and immunohistochemical staining were performed on lung tissues. Lung tomography images of the rats were also examined.

Results

The levels of TGF-β1, HMGB1, NLRP3, and interleukin 1 beta (IL-1β) mRNA expressions increased as a result of PF and subsequently decreased with both ramelteon doses (p ​< ​0.0001). Both doses of ramelteon partially ameliorated the reduction in the peribronchovascular thickening, ground-glass appearances, and reticulations, and the loss of lung volume.

Conclusions

The severity of fibrosis decreased with ramelteon application. These effects of ramelteon may be associated with NLRP3 inflammation cascade.

Purpose

The effect of urotensin II (U-II), a powerful endogenous vasoconstrictor substance, on the immune system and its mediators is very important.

It was herein aimed to demonstrate the possible relationship between the calcineurin/nuclear factor of activated T-cells cytoplasmic 1/interleukin-2 (CaN/NFATc/IL-2) pathway and urotensin receptors (UTRs) in inflammatory response due to lipopolysaccharide (LPS).

Methods

An LPS-induced inflammation model was used on the human umbilical vein endothelial cells (HUVEC) cell line and drugs were applied accordingly, forming the following groups: Control Group, LPS Group, Agonist Group (10⁻⁸ ​M U-II), Antagonist Group (10⁻⁶ ​M palosuran), Tacrolimus (TAC) Group (10 ​ng/mL FK-506), Agonist ​+ ​TAC Group, and Antagonist ​+ ​TAC Group. Gene expression analyses were performed using real-time polymerase chain reaction (RT-PCR).

Results

In the analysis of the cell viability at 48 and 72 ​h, there was a decrease in the Agonist Group, while in the Agonist ​+ ​TAC Group, the cell viability increased. In the Antagonist Group, cell viability was maintained when compared to the LPS Group, while in the TAC Group, this effect was reduced. The mRNA expression levels of UTR, CaN, NFATc, IL-2 receptor (IL-2R), IL-6 and nuclear factor kappa B (NF-κB) were higher in the LPS Group than in the Control Group, and even the UTR, CaN, NFATc, IL-2R were higher with agonist administration. This effect of the agonist was shown to be completely mitigated in the presence of the CaN inhibitor.

Conclusion

U-II and its receptors can perform key functions regarding the endothelial cell damage via the CaN/NFATc/IL-2 pathway.

Heat shock proteins (HSPs) represent cellular chaperones that are classified into several families, including HSP27, HSP40, HSP60, HSP70, and HSP90. The role of HSPs in the cell includes the facilitation of protein folding and maintaining protein structure. Both processes play crucial roles during stress conditions in the cell such as heat shock, degradation, and hypoxia. Moreover, HSPs are important modulators of cellular proliferation and differentiation, and are strongly associated with the molecular orchestration of carcinogenesis. The expression and/or activity of HSPs in cancer cells is generally abnormally high and is associated with increased metastatic potential and activity of cancer stem cells, more pronounced angiogenesis, downregulated apoptosis, and the resistance to anticancer therapy in many patients. Based on the mentioned reasons, HSPs have strong potential as valid diagnostic, prognostic, and therapeutic biomarkers in clinical oncology. In addition, numerous papers describe the role of HSPs as chaperones in the regulation of immune responses inside and outside the cell. Importantly, highly expressed/activated HSPs may be inhibited via immunotherapeutic targets in various types of cancers. The aim of this work is to provide a comprehensive overview of the relationship between HSPs and the tumor cell with the intention of highlighting the potential use of HSPs in personalized cancer management.

Purpose

This study retrospectively investigated the association between the level of human leukocyte antigen (HLA) mismatches (MMs), direction of disparities and differences at particular HLA locus on clinical outcomes of hematopoietic stem cell transplantation (HSCT). Investigated outcomes were overall survival (OS) and disease-free survival (DFS), graft-versus-host disease (GvHD), relapse and non-relapse mortality (NRM).

Patients and methods

Study cohort included 108 adult patients transplanted between 2011 and 2021 and their 9/10 mismatched unrelated donors (MMUD). All individuals were typed for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci using Polymerase Chain Reaction-Sequence Specific Primers, PCR-Sequence Based Typing and Next-Generation Sequencing. All statistical analyses were done in the MedCalc software, version 19.2.6.

Results

Patients with MMs at HLA-B locus demonstrated worse OS (P ​= ​0.0440, HR ​= ​2.00, n ​= ​20). Absence of HLA-DRB5 was associated with a higher incidence of GvHD (P ​= ​0.0112, HR ​= ​1.93, n ​= ​67). A lower incidence of GvHD was observed in patients with HLA class II MMs compared to patients with HLA class I MMs (P ​= ​0.0166, HR ​= ​1.94, n ​= ​29). Finally, analysis of PIRCHE score (PS) impact revealed that patients with HLA class II PS ​> ​10 in GvH direction showed higher incidence of GvHD compared to patients with HLA class II PS ​< ​10 (P ​= ​0.0073, HR ​= ​2.01, n ​= ​55).

Conclusion

Obtained results undisputedly indicate the necessity to further investigate this matter on a larger patient group, with focus on specific HLA alleles to define precisely priority criteria for selecting the best donor for all patients, thus improving the outcome of HSCT with an MMUD.

Purpose

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a complication of COPD that typically necessitates intensified treatment and hospitalization. It is linked to higher morbidity, mortality and healthcare spending. Assessment of therapy response for AECOPD is difficult due to the variability of symptoms and limitations in current measures. Hence, there is a need for new biomarkers to aid in the management of AECOPD in acute care settings.

Materials and methods

Fifteen hospitalized AECOPD patients (GOLD 3–4) were enrolled in this study. Treatment response was assessed daily through clinical evaluations and by monitoring tidal breathing biomarkers (respiratory rate [RR], expiratory time [T_ex], inspiratory time [T_in], expiratory pause [T_rst], total breath time [T_tot]), using a novel, wearable nanosensor-based device (SenseGuard™).

Results

Patients who showed significant clinical improvement had substantial changes in ΔT_ex/T_tot (+14%), ΔT_rst/T_tot (−18%), and ΔT_in/T_ex (+0.09), whereas patients who showed mild or no clinical improvement had smaller changes (+5%, +3%, and −0.03, respectively). Linear regression between change in physician's assessment score and the median change in tidal breathing parameters was significant for T_in/T_ex (R² ​= ​0.449, ∗p ​= ​0.017), T_ex/T_tot (R² ​= ​0.556, ∗p ​= ​0.005) and T_rst/T_tot (R² ​= ​0.446, ∗p ​= ​0.018), while no significant regression was observed for RR, T_in/(T_rst ​+ ​T_ex) and T_in/T_tot.

Conclusions

Our study demonstrates the potential of the SenseGuard™ to monitor treatment response in AECOPD patients by measuring changes in tidal breathing biomarkers, which were shown to be associated with significant changes in the patients' respiratory condition as evaluated by physicians. However, further large-scale clinical studies are needed to confirm these findings.

Purpose

Commonly used technologies for visual pattern stimulation cannot operate in a magnetic resonance imaging room because they can interfere with the operation of the scanner and are vulnerable to its electromagnetic and magnetic fields. The aim of this single-center prospective observational study was to introduce a novel, structurally uncomplicated, easy-to-maintain, patterned edge-illuminated display (PEID) device for visual pattern-reversal stimulation, compare it with a commonly used cathode ray tube screen, and verify the equivalence of quantitative assays.

Materials and methods

The left and right eyes of 36 healthy participants with undilated pupils were examined on a commercial visual evoked potential (VEP) apparatus and on the PEID device, where pattern-reversal transient VEPs were elicited by checkerboard stimuli with large (0.89°; 0.86°–0.92°) and small (0.21°; 0.20°–0.23°) checks.

Results

The PEID device demonstrated the required reliability and dynamic characteristics, as well as precise time-locking required for a VEP diagnosis. The results of Deming's correlation analysis showed that both the commercial cathode ray tube monitor and the PEID device produced identical VEP results within the context of experimental uncertainty. The standard deviation of Deming's regression may indicate the uncertainty of the VEPs measured in clinical practice. The Bland-Altman analysis of the mean showed no significant difference in the amplitude and peak time of VEPs measured on the PEID device compared to that of the commercial cathode ray tube monitor.

Conclusions

The presented PEID device meets all the required standards and can be easily installed in various types of commercial magnetic resonance imaging scanners.

Purpose

The primary limiting factor in achieving cures for patients with cancer, particularly ovarian cancer, is drug resistance. The mechanisms of drug resistance of cancer cells during chemotherapy may include compounds of the extracellular matrix, such as the transforming growth factor-beta-induced protein (TGFBI). In this study, we aimed to analyze the TGFBI gene and protein expression in different sensitive and drug-resistant ovarian cancer cell lines, as well as test if TGFBI can be involved in the response to topotecan (TOP) at the very early stages of treatment.

Materials and methods

In this study, we conducted a detailed analysis of TGFBI expression in different ovarian cancer cell lines (A2780, A2780TR1, A2780TR2, W1, W1TR, SKOV-3, PEA1, PEA2 and PEO23). The level of TGFBI mRNA (QPCR), intracellular and extracellular protein (Western blot analysis) were assessed in this study.

Results

We observed upregulation of TGFBI mRNA in drug-resistant cell lines and estrogen-receptor positive cell lines, which was supported by overexpression of both intracellular and extracellular TGFBI protein. We also showed the TGFBI expression after a short period of treatment of sensitive ovarian cancer cell lines with TOP.

Conclusion

The expression of TGFBI in ovarian cancer cell lines suggests its role in the development of drug resistance.