Advances in medical sciences最新文献

Purpose

Breast cancer is the most common malignancy with high recurrence and mortality rates in women. There are still insufficient biomarkers to predict disease prognosis. Therefore, the present study aimed to investigate the clinical significance of postoperative hematologic parameters and their derivatives in patients with breast cancer who underwent tumor resection.

Patients and methods

The clinicopathological and laboratory data of 90 female breast cancer patients who underwent surgical treatment in the Greater Poland Cancer Center in Poznan from December 2015 to November 2017 were retrospectively analyzed. Postoperative hematologic parameters, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), monocyte-to-red blood cell ratio (MRR), lymphocyte-to-red blood cell ratio (LRR), platelet-to-red blood cell ratio (PRR) were evaluated in recurrence and non-recurrence group. Receiver-operating characteristic (ROC) curve analysis was used to assess the optimal cutoff value of postoperative hematologic parameters for tumor recurrence. The association of postoperative hematologic parameters with disease-free survival (DFS) was investigated by the Kaplan-Meier method and Cox regression analysis.

Results

Patients with local, regional, or distant metastases accounted for 14% of the total. The postoperative monocyte count and MRR were significantly elevated, whereas postoperative LMR was statistically decreased in the recurrence group. Univariate and multivariate Cox analysis revealed that postoperative LMR ≤3.044 and postoperative MRR >0.1398 were associated with significantly shorter DFS.

Conclusion

Our results revealed that both postoperative LMR and MRR are independent predictors of DFS in breast cancer patients. Large-scale prospective investigations are needed to validate our findings.

Purpose

Metformin (MET), a first-line treatment for type 2 diabetes mellitus, restores ovarian function in women with polycystic ovary syndrome. MET has been shown to increase the rate of success for in vitro fertilization when utilized in assisted reproductive technologies. This study was designed to examine the impact of MET on ovarian function and fertility in a mouse model of galactose-induced premature ovarian insufficiency (POI). We further investigated the underlying mechanisms.

Materials and methods

Female mice were divided into 4 groups: saline, d-galactose, d-galactose ​+ ​MET, and MET. Body weight, ovarian index, and fertility were assessed. The hormonal profile was done. Advanced glycation end products (AGEPs), receptor for advanced glycation end products (RAGE), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), forkhead box O3a (FOXO3a) expression were measured. Ovarian follicle counting and morphology were analyzed. Immunohistochemistry of cleaved caspase-3 expression was performed.

Results

Our findings demonstrated that MET reversed irregularities in the estrus cycle, enhanced the ovarian index, and improved the abnormal levels of hormones and AGEs induced by d-galactose. Furthermore, the expression levels of PI3K, Akt, FOXO3a, and RAGE were upregulated with d-galactose. However, MET attenuated their expression levels. The primordial follicles ratio was improved, whereas atretic follicles and apoptotic-related cleaved caspase-3 expression were decreased in the d-galactose ​+ ​MET group compared to the d-galactose group.

Conclusion

This study demonstrates that MET partially rescued ovarian dysfunction and apoptosis induced by d-galactose via a mechanism involving PI3K-Akt-FOXO3a pathway. Our finding proposed that MET may be a promising alternative treatment for POI.

Purpose

Acute heart failure (AHF) is a serious condition that requires prompt diagnosis and management. To optimize patient care, clinicians need a reliable, non-invasive method to assess hemodynamic parameters and total body congestion. Currently, no standardized technology is widely used for this purpose. However, NICaS technology, which measures hemodynamic parameters based on regional bioimpedance, has shown promise in monitoring AHF patients in a non-invasive and reliable manner. In this study, researchers aimed to evaluate the usefulness of NICaS technology in predicting patients' outcome in Caucasian and Asian AHF patients presenting to the emergency department (ED).

Patients and methods

The study included 40 Caucasian patients from Italy (group A) and 71 Asian patients from Indonesia and Singapore (group B) with a diagnosis of AHF in the ED. The study compared data from NICaS parameters, clinical findings, laboratory, and radiological results with short-term events.

Results

In group A, NICaS data at ED arrival significantly predicted 30-day cardiovascular mortality and rehospitalization. At discharge, a value of cardiac output obtained using NICaS was a significant predictor for 30-day rehospitalization. In group B, NICaS variables, total peripheral resistance index on admission and during 48–72 ​h had prominent AUC compared to clinical congestion score and NT-proBNP in predicting mortality and rehospitalization.

Conclusions

The results indicate that NICaS technology offers a simple, non-invasive, and reliable method of assessing cardiac hemodynamics and congestion in AHF patients. These measurements may enhance diagnosis, tailor management plans, stratify risk, and predict outcomes in both Caucasian and Asian patients.

Purpose

Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of fibrinolytic systems. The effect of PAI-1 on inflammatory response is still inconsistent. Our study was conducted to investigate its effects on inflammation to clarify the role of PAI-1 in acute lung injury (ALI) induced by lipopolysaccharide (LPS).

Material and methods

ALI models were established in wild-type (WT) and PAI-1 knockout (KO) mice by LPS intervention for 48 ​h. Lung histopathology, wet-dry ratio, total cell count and TNF-α concentration in bronchoalveolar lavage fluid (BALF), and inflammation related proteins were detected. Flow cytometry was used to sort neutrophils, macrophages, regulatory T cells (Treg) and T helper cell 17 (Th17). RNA sequencing was performed to find differentially expressed genes. Masson staining and immunohistochemistry were used to analyze pulmonary fiber deposition and proliferation.

Results

Compared with ALI (WT) group, the wet-dry ratio, the total number of BALF cells, the concentration of TNF-α in BALF, and the expression of pp65 in the lung tissue was increased in ALI (PAI-1 KO) group, with increased proportion of neutrophils, decreased proportion of macrophages and decreased proportion of Treg/Th17 in the lung tissue. Collagen fiber deposition and PCNA expression were lighter in ALI (PAI-1 KO) group than ALI (WT) group. PPI analysis showed that PAI-1 was closely related to TNF, IL-6, IL-1β, Smad2/3 and mainly concentrated in the complement and coagulation system, TNF-α and IL-17 signaling pathways.

Conclusions

PAI-1 KO could aggravate ALI induced by LPS at 48 ​h. PAI-1 may be an important target to improve the prognosis of ALI.

Purpose

Bipolar affective disorder (BP) causes major functional impairment and reduced quality of life not only for patients, but also for many close relatives. We aimed to investigate mRNA levels in BP patients to find differentially expressed genes linked to specific clinical course variants; assuming that several gene expression alterations might indicate vulnerability pathways for specific course and severity of the disease.

Materials

We searched for up- and down-regulated genes comparing patients with diagnosis of BP type I (BPI) vs type II (BPII), history of suicide attempts, psychotic symptoms, predominance of manic/hypomanic episodes, and history of numerous episodes and comorbidity of substance use disorders or anxiety disorders. RNA was extracted from peripheral blood mononuclear cells and analyzed with use of microarray slides.

Results

Differentially expressed genes (DEGs) were found in all disease characteristics compared. The lowest number of DEGs were revealed when comparing BPI and BPII patients (18 genes), and the highest number when comparing patients with and without psychotic symptoms (3223 genes). Down-regulated genes identified here with the use of the DAVID database were among others linked to cell migration, defense response, and inflammatory response.

Conclusions

The most specific transcriptome profile was revealed in BP with psychotic symptoms. Differentially expressed genes in this variant include, among others, genes involved in inflammatory and immune processes. It might suggest the overlap of biological background between BP with a history of psychotic features and schizophrenia.

Purpose

Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor beta superfamily and is faintly expressed under healthy conditions. GDF-15 is markedly elevated in a variety of diseases, including coronary artery disease (CAD), atrial fibrillation and heart failure. Here, we aimed to investigate the association of GDF-15 with the extent and severity of CAD in patients with stable CAD.

Methods

We enrolled 129 patients undergoing coronary angiography for the evaluation of stable CAD in the study. SYNTAX and SYNTAX II PCI/CABG scores were calculated. The CAD (+) study group was also stratified into two groups (high and low GDF-15) with respect to the mean GDF-15 value. Correlation and regression analyses were performed for further evaluation.

Results

Of the 129 patients, 75 had CAD. GDF-15 values were higher in the CAD (+) group (p ​< ​0.001). The two groups were compared according to a cut-off value of 2451.77. SYNTAX and SYNTAX II PCI/CABG scores were significantly associated with the high GDF-15 group (p ​< ​0.001). Additionally, correlation analysis showed a strong positive correlation between GDF-15 and SYNTAX (r: 0.859, p ​< ​0.001), SYNTAX II PCI (r: 0.921, p ​< ​0.001) and SYNTAX II CABG (r: 0.874, p ​< ​0.001) scores. Multivariate analysis identified GDF-15 as an independent predictor of CAD.

Conclusion

GDF-15 is an independent predictor of CAD and is associated with CAD severity in terms of SYNTAX, SYNTAX II PCI and SYNTAX II CABG scores.

Background

Hypocalcaemia predicts coronavirus disease 2019 (COVID-19) severity and mortality. We hypothesized an association between respiratory alkalosis secondary to hypoxia and low ionised calcium (iCa) concentration in patients with COVID-19.

Methods

Arterial blood gas samples taken from January 2019 to March 2021 were retrospectively matched with infection status. Principal components regression was undertaken to determine the correlation between pH, partial pressure arterial oxygen (PaO₂), partial pressure arterial carbon dioxide (PaCO₂), and iCa.

Results

We included 4056 patients (300 COVID-19 detected, 19 influenza detected), corresponding to 5960 arterial blood samples. The COVID-19 detected group had a statistically significantly lower iCa, PaO₂ and PaCO₂, and more alkalotic pH than infection-free groups. The influenza group had a lower iCa and PaCO₂, higher PaO₂, and a more alkalotic pH than infection-free groups, but these differences were non-significant. Principal components regression revealed that pH, PaCO₂, and PaO₂ explain just 2.72 % of the variance in iCa. An increase in pH by 1 unit was associated with an iCa reduction of 0.141 ​mmol/L (p ​< ​0.0001).

Conclusion

Reduction in iCa concentration in patients with COVID-19 is not associated with pH derangement. Influenza infection was associated with a minor reduction in iCa in our small sample, a hitherto unreported finding, although statistical significance was not demonstrated.

Glycation is a physiological process that determines the aging of the organism, while in states of metabolic disorders it is significantly intensified. High concentrations of compounds such as reducing sugars or reactive aldehydes derived from lipid oxidation, occurring for example in diabetes, atherosclerosis, dyslipidemia, obesity or metabolic syndrome, lead to increased glycation of proteins, lipids and nucleic acids. The level of advanced glycation end-products (AGEs) in the body depends on rapidity of their production and the rate of their removal by the urinary system. AGEs, accumulated in the extracellular matrix of the blood vessels and other organs, cause irreversible changes in the biochemical and biomechanical properties of tissues. As a consequence, micro- and macroangiopathies appear in the system, and may contribute to the organ failure, like kidneys and heart. Elevated levels of AGEs also increase the risk of Alzheimer's disease and various cancers. In this paper, we propose a new classification due to modified amino acid residues: arginyl-AGEs, monolysyl-AGEs and lysyl-arginyl-AGEs and dilysyl-AGEs. Furthermore, we describe in detail the effect of AGEs on the pathogenesis of metabolic and old age diseases, such as diabetic complications, atherosclerosis and neurodegenerative diseases. We summarize the currently available data on the diagnostic value of AGEs and present the AGEs as a therapeutic goal in a wide range of medical problems, including SARS-CoV-2 infection and so-called long COVID.

Purpose

The purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery.

Materials/methods

Between 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40–50 Gy/20–25 fractions). SBRT dose was 30–40 ​Gy in 5 fractions for patients treated with SBRT alone and 25–32 ​Gy in 4–5 fractions for those treated with SBRT ​+ ​WBRT. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Response was also assessed using RECIST guidelines.

Results

Median follow-up was 32 (range: 3.4–70.4) months. Imaging at median 2.2 (0.6–8.1) months post-SBRT showed median 43.2 ​% (range: 2–100 ​%) decrease in the largest diameter and median 68.7 ​% (range: 27.9–100 ​%) SUV reduction. There were 3 cases of local progression at 8.7–10.6 months. Estimated LC was 100 ​% at 6 months and 71.6 ​% at 12, 24 and 36 months.

Estimated median OS was 100 ​% at 6 months, 76.9 ​% at 12 months, and 61.5 ​% at 24 and 36 months. Acute toxicity (n ​= ​13; 92.9 ​%) included grade (G)1 (n ​= ​8), G2 (n ​= ​4), and G4 (necrosis; n ​= ​1). Late toxicity included G2 edema (n ​= ​1) and G4 necrosis (n ​= ​2, including 1 consequential late effect). Only patients treated with SBRT ​+ ​WBRT experienced acute/late G4 toxicity, managed with resection or steroids.

Conclusions

SBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n ​= ​2) occurred in the SBRT ​+ ​WBRT group, it was successfully salvaged.

Uterine leiomyomas (ULs) are the most common benign smooth muscle cell steroid-dependent tumors that occur in women of reproductive age. Progesterone (P4) is a major hormone that promotes the ULs development and growth. P4 action in ULs is mediated mainly by its nuclear progesterone receptors (PGRs), although rapid non-genomic responses have also been observed. Data on the membrane progesterone receptors (mPRs) regulated signaling pathways in ULs in the available literature is still very limited. One of the essential characteristics of ULs is the excessive production of extracellular matrix (ECM). P4 has been shown to stimulate ECM production and collagen synthesis in ULs. Recent research demonstrated that, despite their benign nature, ULs may present with abnormal vasculature. P4 has been shown to regulate angiogenesis in ULs through the upregulation of vascular endothelial growth factor (VEGF) and by controlling the secretion of permeability factors. This review summarizes the key findings regarding the role of PGRs and mPRs in ULs, especially highlighting the potential ECM and angiogenesis modulation by P4. An increased understanding of this mechanistic role of nuclear and specifically mPRs in the biology of P4-modulated ECM and angiogenesis in the growth of ULs could turn out to be fundamental for developing effective targeted therapies for ULs.