Advances in Clinical and Experimental Medicine最新文献

Background: Preeclampsia is a serious pregnancy complication with significant maternal and fetal morbidity. Mitophagy plays a crucial role in its pathogenesis. The importance of this study lies in evaluating the role of parkin in preeclampsia, which may offer new insights into the management of this disease.

Objectives: This study was designed to evaluate the role of parkin in preeclampsia.

Material and methods: To induce a preeclampsia model, pregnant female rats were administered N-nitro-L-arginine methyl ester (L-NAME) subcutaneously at a dose of 50 mg/(kg·day) starting on gestational day 14 for 7 consecutive days. Uteroplacental tissues were then collected, and chorionic trophoblast cells were isolated. Systolic blood pressure (SBP) and urine protein content were measured on days 12 and 20 of pregnancy. Hematoxylin-eosin (H&E) staining and TUNEL staining were employed to assess pathological changes and apoptosis in uteroplacental tissues, respectively. Reverse transcription polymerase chain reaction (RT-qPCR) and western blot analysis were performed to evaluate mRNA and protein expression levels associated with cellular function, mitophagy and the PINK1/parkin signaling pathway.

Results: Compared to the negavtive control (NC) group, rats in the model group showed elevated SBP and urine protein levels (p < 0.01). Chorionic trophoblast cells exhibited substantial damage, with significantly increased levels of apoptosis and autophagy. Moreover, parkin mRNA and protein expression levels were markedly upregulated in the model group. Overexpression of parkin in chorionic trophoblast cells enhanced apoptosis and mitophagy, while the autophagy inhibitor 3-methyladenine (3-MA) significantly alleviated the damage caused by overexpression of parkin.

Conclusions: Parkin aggravates the symptoms of preeclampsia by increasing mitophagy and apoptosis.

Background: The two-drug regimen Kd-70 (carfilzomib at a dose of 70 mg/m2 with dexamethasone) is a recommended treatment option for patients with relapsed or refractory multiple myeloma, according to both American and European guidelines. However, aside from the A.R.R.O.W. trial, real-world data on its effectiveness remain limited.

Objectives: We aimed to assess the effectiveness of the two-drug regimen Kd-70 in real-world practice.

Material and methods: We analyzed data from the Polish Ministry of Health registry, which included 412 patients treated with the Kd-70 regimen in Poland.

Results: The overall response rate (ORR) was 67.15%, comparable to the A.R.R.O.W. trial. However, the complete response (CR) rate (5.3%) and very good partial response (VGPR) rate (9.59%) were lower than those reported in the A.R.R.O.W. study. Notably, Kd-70 showed significantly lower efficacy in patients who required treatment for primary resistance or disease progression within the 1st year after diagnosis. In contrast, the number of prior treatment lines did not impact the regimen's effectiveness.

Conclusions: In real-world clinical practice, the Kd-70 regimen demonstrated an ORR comparable to that observed in the A.R.R.O.W. trial. However, the CR and VGPR rates were lower. These findings underscore the need for further investigation into factors influencing treatment outcomes in this patient population.

Background: The coronavirus disease 2019 (COVID-19) pandemic has significantly accelerated the development and use of new healthcare technologies. While younger individuals may have been able to quickly embrace virtual advancements, older adults may still have different needs in terms of health communication.

Objectives: To identify areas of interest and preferred sources of information related to the COVID-19 pandemic among older adults and to verify their eHealth competencies.

Material and methods: The study was conducted between February 2022 and July 2022. It included listeners from the University of the Third Age (U3A) and younger students. Both groups received information about the HealthBuddy+ chatbot, a questionnaire that addressed respondents' interests about COVID-19, and the PL-eHEALS (eHealth Literacy Scale) questionnaire to measure their eHealth competencies.

Results: There were 573 participants in the study (U3A listeners - 303 participants, median age: 73 years (interquartile range (IQR): 69-77); young adult students - 270, median age: 24 years (IQR: 23-24). The primary source of information about COVID-19 for older adults was television (84.5%), and for younger adults, internet (84.4%). Among the older adults, only 17% ever interacted with a chatbot (younger adults - 78% respectively), and 19% considered it a trustworthy source of information on COVID-19 compared to 79% of younger respondents. Older adults and younger adults in our study were most interested in COVID-19 treatment methods (45.5% and 69.3%, respectively), symptoms of the disease (36.6% and 35.2%, respectively) and chronic diseases coexisting with COVID-19 (35.0% and 51.5%, respectively). However, their eHealth competencies were generally low (median (Me): 34; IQR: 30-39) compared to younger adults (Me: 42; IQR: 40-47).

Conclusions: Health education for older adults should be appropriately tailored to their current needs and differentiated. The level of eHealth competencies of older adults suggests that much work remains to narrow the gap between the eHealth competencies of the younger and older generations.

Background: Non-alcoholic fatty liver disease (NAFLD) is currently a public health problem that affects many people worldwide. New-generation dietary agents can contribute to disease control. Also, prediction of liver disease activity with serum markers is an important factor to reduce the need for liver biopsies.

Objectives: The aim of this study was to compare the effects of 20 mg/kg green coffee bean extract (GCBE, standardized to 10 mg/kg chlorogenic acid), 10 mg/kg chlorogenic acid (CA) and 50 mg/kg CA on NAFLD activity score (NAS). We also aimed to create a NAS prediction model as an alternative to liver biopsies.

Material and methods: Male Wistar rats were fed either a high-fat high-cholesterol (HFHC) diet (NAFLD groups, n = 32) or a normal diet (control groups, n = 24). Green coffee bean extract (20 mg/kg) and CA (10 mg/kg and 50 mg/kg) were given by daily oral gavage. At the end of the study, blood samples and liver tissues were collected. Biochemical parameters, glyoxalase 1 (GLO1) and oxidative stress parameters were analyzed. An experienced histopathologist graded NAS.

Results: Green coffee bean extract and 50 mg/kg CA significantly reduced NAS (p < 0.01 and p < 0.001, respectively). HFHC-diet induced NAFLD was associated with higher serum GLO1 levels (p < 0.001). Serum malondialdehyde (MDA) levels were positively correlated with NAS while GLO1 was negatively correlated with NAS (p < 0.001, r = 0.698; p < 0.05, r = -0.367, respectively). Serum MDA and triglyceride were found to be statistically significant in predicting NAS (p < 0.001).

Conclusions: Our study suggests that GCBE and CA can both ameliorate the development of NAFLD. Also, low-dose GCBE and high-dose CA showed similar hepatoprotective effects. Increased GLO1 in NAFLD may be a defense mechanism which is enhanced by GCBE and CA. Moreover, serum MDA and triglyceride levels are promising in NAS prediction.

Background: Salvianolic acid F (SAF), an important water-soluble monomeric component, is derived from the herbal medicine Salvia miltiorrhiza (SM) Bunge. Although SAF has been suggested to suppress various cancers, its role in ovarian cancer (OC) and the underlying mechanisms remain largely unclear.

Objectives: This study aimed to investigate the effects of SAF on OC cell growth, invasion, migration, and apoptosis, as well as to elucidate the underlying mechanisms, including those involving the EP300/PI3K/AKT signaling pathway.

Material and methods: In vitro cell culture experiments were conducted to assess the effects of SAF on the proliferation, migration, invasion, and apoptosis of OVCAR-3 (Ovarian Cancer Cell Line 3) and SK-OV-3 (Sloan-Kettering Ovarian Cancer 3) cells. Network pharmacology was further employed to explore SAF's impact on OC and to elucidate the potential underlying mechanisms. The EP300-mediated PI3K/AKT signaling pathway was selected for validation to confirm SAF's effects on inducing apoptosis and inhibiting cell proliferation in these OC cell lines.

Results: Salvianolic acid F suppressed the growth, invasion and migration of SK-OV-3 and OVCAR-3 cells, and induced apoptosis. A network pharmacology analysis of SAF's effects on OC identified core targets, TP53, EP300, STAT3, MMP9, NFKB1, HIF1A, and PTGS2, through protein-protein interaction (PPI) network analysis using the STRING database. Salvianolic acid F inhibited EP300 expression in SK-OV-3 cells, reduced the p-PI3K/PI3K ratio, and increased both the Bax/Bcl-2 ratio and the cleaved caspase-3/caspase-3 ratio in OVCAR-3 and SK-OV-3 cells. However, the addition of A485, an EP300 inhibitor, did not further enhance the effects of SAF.

Conclusions: Salvianolic acid F inhibited OC cell growth, migration and invasion while promoting apoptosis. The EP300/PI3K/AKT pathway is a key mechanism through which SAF regulates OC progression. Additionally, SAF may represent a promising candidate drug for treating OC.

Strengthening primary healthcare (PHC) research is vital to address the demands of a rapidly changing health landscape. Leadership, infrastructure, and sufficient funding have been discussed as key factors in expanding PHC research capacity. This editorial aims to highlight emerging research priorities in a world increasingly affected by crises such as war, conflict, and climate change. Research on suffering, meaning, hope, and compassion represents a promising and necessary new frontier in PHC. This field urgently needs the attention of academic institutions and funding bodies committed to strengthening primary care and family medicine.

Background: Emergency medical teams are a crucial component of healthcare systems, routinely providing essential care to pregnant patients in various situations.

Objectives: To evaluate the rate and outcomes of out-of-hospital deliveries attended by Emergency Medical Services (EMS) in Poland and identify areas for improvement in the care provided by emergency medical teams.

Material and methods: This retrospective study was based on 41,335 EMS emergency calls to women in advanced pregnancy, of which 879 births were delivered directly by medical teams between January 2018 and December 2022. Data were obtained from the Polish National Monitoring Center for Emergency Medical Services, encompassing all EMS interventions in Poland.

Results: The study involved 879 EMS team interventions for pregnant women, with an average patient age of 29.87 years. Most patients were in their 2nd pregnancy (28.26%) and delivering for the 2nd time (25.77%). The postnatal condition of newborns, assessed using the Apgar score, was missing in 408 cases (46.52%) due to incorrect completion of documentation. Emergency Medical Services teams, predominantly P-type (basic) teams, handled 69.78% of deliveries, while S-type (specialist) teams were involved in 30.22% of cases. Medical procedures often performed during childbirth included manual assistance in spontaneous delivery, pulse oximetry, physical examination, examination of systemic blood pressure, obtaining peripheral intravenous access, and gynecological examination.

Conclusions: Given the rate of encountered cases and the gaps identified in medical documentation, there is merit in potentially implementing a dedicated form to be completed by medical teams when caring for a pregnant patient. Ongoing training and enhancements in the range of assistance provided to the mother and newborn are imperative for ensuring appropriate care.

Transcranial direct current stimulation (tDCS) has emerged as a widely accessible, noninvasive technique capable of modulating cortical excitability. A rapidly expanding body of sports-science literature suggests that it can produce modest but measurable gains in endurance, strength, skill acquisition, and perceived exertion. This editorial reviews the physiological mechanisms underlying tDCS, evaluates the evidence for its ergogenic effects, and situates the technology within the broader framework of "neurodoping". Applying the 2021 World Anti-Doping Agency (WADA) Code, I argue that tDCS already satisfies 2 of the 3 criteria for prohibition - namely, potential performance enhancement and violation of the spirit of sport - while failing the 3rd criterion, as standard protocols pose minimal health risk. This editorial also considers practical and ethical counterarguments to a ban, including tDCS's low cost, relative safety, requirement for continued training effort, and the near-impossibility of detection or enforcement. Drawing parallels with accepted performance aids such as mindfulness, nutrition and altitude tents, this editorial concludes that outright prohibition could drive use underground and impede open scientific scrutiny. Instead, it advocates rigorous long-term safety monitoring, transparent research, and nuanced policy development that distinguishes therapeutic from performance applications. Ultimately, it frames tDCS as a "still-legal" yet ethically contested innovation at the frontier of sports technology, urging stakeholders to balance principles of fair play with scientific evidence as the debate over neurodoping continues to evolve.

Background: Patients with aortic arch lesions involving the left subclavian artery (LSA) usually require endovascular surgery. The Castor single-branch stent graft provides a targeted solution for such cases, with potential benefits enhanced by the direction-turnover and unwrapping techniques.

Objectives: To evaluate the safety, efficacy and short-term outcomes of the direction-turnover joint unwrapping techniques combined with a Castor single-branch stent graft in treating aortic arch lesions involving the LSA.

Material and methods: From January 2022 to June 2023, 18 patients with aortic arch and LSA lesions underwent Castor stent graft placement at Binzhou Medical University Hospital (Shangdong, China). Preoperative and postoperative imaging with computed tomography angiography (CTA) was used to assess stent placement and efficacy at 1, 3, 6, and 12 months post-surgery.

Results: All 18 patients successfully received the stent graft without intraoperative complications, stent migration or residual shunting. Postoperative imaging confirmed accurate stent placement with no evidence of thrombosis or endoleaks.

Conclusions: The direction-turnover and unwrapping techniques improve the accuracy and safety of Castor stent graft placement, effectively reducing guidewire entanglement and enhancing procedural success. These techniques show promise for broader application in complex aortic arch interventions.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune inflammatory disease with a multisystem manifestation and a variety of clinical symptoms. Over the last decades, the prognosis and life expectancy of patients with SLE improved significantly due to the implementation of corticosteroids combined with immunosuppressive agents. Nevertheless, the use of these medications is often associated with the occurrence of serious side effects and additional deterioration of organ function. Therefore, developing and implementing novel therapies that are both safer and more effective in managing disease is crucial. For a long time, European Alliance of Associations for Rheumatology (EULAR) recommended only 2 biological agents in the treatment of SLE: belimumab and rituximab. However, in 2023, anifrolumab, an interferon (IFN) receptor inhibitor, and voclosporin, a novel calcineurin inhibitor, appeared in new SLE treatment guidelines. In addition, several biological agents are targeting different cells or cytokines that are being evaluated in phase II and III clinical trials. Apart from that, experimental therapies such as targeting of plasma cells, chimeric antigen receptor T-cell therapy (CAR-T) or stem cell transplantation appear promising in the treatment of the severe forms of SLE.