Advances in Clinical and Experimental Medicine最新文献

Objectives: To assess the effectiveness of HTS in lowering elevated ICP in TBI patients with TBI.

Material and methods: A systematic search was conducted using 4 electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select relevant articles published in peer-reviewed journals. The risk ratio (RR) and mean difference (MD) were calculated, along with their 95% confidence intervals (95% CIs). Heterogeneity was assessed using Cochrane Q, I2 statistics and p-value. RevMan 5.4 was used.

Results: The current meta-analysis included 965 TBI patients from 15 randomized controlled trials (RCTs). We found that HTS was significantly more effective than other ICP-lowering agents with RR of 0.74 (95% CI: 0.58-0.94) for reduction of elevated ICP; RR = 0.57 (95% CI: 0.40-0.81) for all-cause mortality; RR = 0.68 (95% CI: 0.49-0.95) for rate of adverse hypernatremia; RR = 0.73 (95% CI: 0.60-0.88) for substantial change in the Glasgow Outcome Scale (GOS) score and shorter period of hospital stay with MD of -1.26 (95% CI: -2.30 to -0.21).

Conclusion: We found that HTS is considerably effective in reducing elevated ICP with improvement in long-term neurological functions, all-cause mortality, rate of hypernatremia, and length of hospital stay in TBI patients.

Immunotherapy has revolutionized oncology; however, its efficacy remains limited by the immunosuppressive tumor microenvironment (TME). This editorial synthesizes recent advances demonstrating how rationally designed combination strategies - particularly those incorporating the transforming growth factor beta/programmed death-ligand 1 (TGF-β/PD-L1) bispecific antibody platform (YM101/BiTP) and the multi-cytokine-armed oncolytic virus VG161 - can overcome resistance mechanisms. By concurrently dismantling immunosuppressive networks, activating innate immunity and remodeling the TME, these approaches show superior preclinical activity across challenging tumor phenotypes. The integration of mechanistic insights with evolving biomarker-driven strategies heralds a new era of personalized combination immunotherapy.

Background: Heart failure (HF) is a chronic condition affecting tens of millions of people worldwide. Despite advances in treatment, its impact on mental health, cognitive function and self-care behaviors remains underexplored, particularly across ejection fraction phenotypes, underscoring the need for comprehensive investigations into these interconnected domains.

Objectives: This prospective cohort study investigated changes in affective symptoms, cognitive functioning and self-care behaviors in patients with HF stratified with ejection fraction (EF) phenotypes over 6 months.

Material and methods: The study included 162 patients aged over 60 years with a diagnosis of HF. Participants were examined at enrollment and after 6 months. The Mini-Mental State Examination (MMSE), the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire-9 (PHQ-9) and the European Heart Failure Self-care Behaviour Scale (EHFScB-9) were used to assess cognitive function, affective symptoms and self-care behaviors.

Results: Cognitive impairment indicated with the MMSE was less severe in patients with mildly-reduced HF (HFmrEF) compared to preserved EF (HFpEF) (MMSE median scores: 28 [interquartile range (IQR): 27-29] vs 27 [IQR: 25-28]; p = 0.008). The HADS showed that severity of depression worsened over 6 months, particularly in the HFpEF group (median scores increased from 1 [IQR: 0-4] to 3 [IQR: 0-6]; p = 0.006). Self-care ability declined in all groups as indicated in the increased EHFSc-9 (poorer self-care) median scores, which changed from 28 [IQR: 21-33] at baseline to 29 [IQR: 23-34] at 6 months (p = 0.035). Additionally, NT-proBNP parameters were higher in the HFrEF group (3437.7 pg/mL [IQR: 1336.33-6226.43) compared to both HFmrEF and HFpEF (2171.2 pg/mL [IQR: 806.65-4033.15] and 977.1 pg/mL [IQR: 576.9-3708.95, respectively, p = 0.001).

Conclusions: Patients with HF showed significant cognitive decline, increased depressive symptoms and reduced self-care over 6 months, with HFpEF patients exhibiting the most pronounced impairments. Differences in outcomes across HF phenotypes highlight the need for tailored diagnostic and therapeutic strategies to address cognitive and emotional challenges in this population.

Background: Dysregulated mitochondrial fission in synovial tissue is a key contributor to the progression of rheumatoid arthritis (RA), and echinacoside (ECH) has been shown to modulate this process in a mouse model of RA.

Objectives: This study aimed to investigate the effects of echinacoside (ECH) on the proliferation and inflammatory response of human fibroblast-like synoviocytes (MH7A cells), and to elucidate the potential underlying mechanisms.

Material and methods: The expression and co-localization of TANK-binding kinase 1 (TBK1) and phosphorylated dynamin-related protein 1 (p-Drp1) in synovial tissues from patients with and without RA were analyzed. MH7A cells were exposed to either ECH or 0.1% dimethyl sulfoxide (DMSO). Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) assay and reactive oxygen species (ROS) expression was detected with dichlorofluorescin (DCFH) staining. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), cyclooxygenase (COX)-2, IL-1β, TANK-binding kinase 1 (TBK1), and Drp1 and the oxidative stress markers NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured using quantitative real-time polymerase chain reaction (qPCR). The mitochondrial morphology was detected with transmission electron microscopy (TEM), and the expression levels of p-TBK1 (S172), TBK1, p-Drp1 (S616), p-Drp1 (S637), and Drp1 were assessed using western blotting.

Results: Compared to tissue from non-RA patients, RA synovial tissue exhibited higher expression and co-localization of TBK1 and phosphorylated Drp1 (p-Drp1). Following ECH treatment, MH7A cell proliferation and inflammatory cytokine secretion were reduced, while the expression of antioxidant stress markers was significantly increased. Furthermore, ECH treatment led to reduced levels of ROS, mitochondrial fragmentation and dysregulated mitochondrial fission in MH7A cells, along with decreased expression of p-TBK1 (Ser172) and p-Drp1 (Ser616), while p-Drp1 (Ser637) levels were increased.

Conclusions: Echinacoside regulates abnormal mitochondrial fission via the TBK1/Drp1 pathway, reducing the proliferation and inflammatory response of MH7A cells.

The U.S. Food and Drug Administration (FDA) recently approved a blood-based biomarker to confirm diagnosis of Alzheimer's disease (AD-BBMs). When used in conjunction with human expertise in the diagnosis of neurocognitive disorder due to Alzheimer's disease (AD), blood-based biomarkers could increase both the accessibility and sustainability of medical practice and research. Indeed, AD-BBMs are likely to be more cost-effective in the long term and conservative calculations performed here suggest that they would have an approx. 10-fold and 36-fold lower carbon footprint compared to cerebrospinal fluid (CSF) lumbar punctures and amyloid positron emission tomography (PET) scans, respectively. Their use will require a careful balance of trade-offs to maximize benefits and minimize harms for current patients, while ensuring the sustainable integration of these tools into healthcare systems so that diagnostic precision remains accessible to present and future generations in an aging global population amid anthropogenic climate change.

Background: Recurrent miscarriage (RM) affects 1-2% of couples. Maternally expressed gene 3 (MEG3) is aberrantly expressed in RM patients.

Objectives: To investigate a novel regulatory mechanism, we examined the miR-204-5p/Specificity protein 1 (SP1)/DNA methyltransferase 1 (DNMT1)/MEG3 axis in the trophoblast cell line HTR-8/SVneo.

Material and methods: Human trophoblast cell line HTR-8/SVneo was used and cells were transfected with siRNA targeting SP1, miR-204-5p mimics, pcDNA3.1-DNMT1, or their negative controls (NCs). The methylation inhibitor, 5-azadC, was used to treat the cells transfected with pcDNA3.1-SP1. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) method was used to examine the relative RNA levels of SP1, DNMT1 and MEG3. Western blot assay was performed to measure the protein levels of SP1 and DNMT1. The dual-luciferase reporter gene assay was used to validate the miR-204-5p bindings to SP1. Functional assays were utilized to assess cell apoptosis, colony formation, migration, and invasion.

Results: SP1 knockdown inhibited DNMT1 and increased MEG3 expression. The expression of MEG3 was enhanced by methylation inhibition through 5-azadC, but SP1 upregulation reversed this effect. SP1 knockdown increased apoptosis and decreased migration and invasion, which was reversed by DNMT1 overexpression. SP1 was targeted and inhibited by miR-204-5p. miR-204-5p also inhibited DNMT1, and enhanced the expression of MEG3. miR-204-5p inhibited cell proliferation, migration and invasion, and promoted apoptosis. Overexpression of SP1 partially reversed these effects by activating DNMT1 and inhibiting MEG3.

Conclusions: miR-204-5p promoted MEG3 expression in trophoblast cells via SP1-mediated DNMT1 inhibition, leading to reduced cell migration, proliferation and invasion, as well as increased apoptosis. This study reveals a novel regulatory axis in trophoblast cells, providing insights into potential regulatory mechanisms in RM.

Background: Inflammatory response is involved in the pathogenesis of herpes zoster (HZ) and postherpetic neuralgia (PHN).

Objectives: This study aimed to evaluate levels of proinflammatory factors at different stages of HZ and PHN.

Material and methods: A total of 154 patients within 72 h of HZ onset and 30 healthy controls were included. Patients were followed up to 90 days. The levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP) were measured at baseline and 90 days. The visual analogue scale (VAS) was used to assess the intensity of pain and PHN patients were divided into mild-to-moderate pain and severe pain group.

Results: Interleukin 6, TNF-α and CRP levels in HZ patients at baseline were significantly higher than in healthy controls and decreased as followed up to 90 days. Moreover, PHN patients had a higher level of IL-6, TNF-α or CRP at baseline and 90 days than non-PHN patients. In addition, PHN patients in the severe pain group had a notably higher baseline or 90-day IL-6, TNF-α and CRP level than in the mild-to-moderate pain group. However, the changes of IL-6, TNF-α and CRP levels between 90 days and baseline were significantly less pronounced in the severe pain group than in the mild-to-moderate pain group.

Conclusions: The levels of proinflammatory cytokines were higher in HZ and PHN patients and associated with pain intensity in PNH patients. These findings suggest that repeated measurements of serum proinflammatory cytokines may aid in clinical management and guide anti-inflammatory treatment strategies.

Currently, there is no doubt that hepatitis C virus (HCV) infection is a systemic disease affecting not only the liver but also a range of other organs - extrahepatic manifestations (EHMs). Extrahepatic manifestations usually occur concurrently with liver disease, primarily have an immunological basis, and/or are a consequence of the direct impact of HCV on virtually all organs. The scope of the problem is significant; it has been shown that 30-40% of HCV-infected individuals are affected, which aligns with our own observations. Viral elimination (either spontaneous HCV clearance or as a result of pharmacotherapy) is crucial for the patient's prognosis, both in terms of liver disease and EHM. Achieving a sustained virological response (SVR) only in many cases of EHMs is associated with remission of clinical symptoms of EHMs.

Background: Hepatic stellate cell (HSC) activation is a critical factor in the development of liver fibrosis. Recent research indicates that mesoderm/mesenchyme homeobox 1 (Meox1) contributes to fibrosis in organs like the skin and heart.

Objectives: To investigate the potential impact of Meox1 on HSC activation and provide an available target for hepatic fibrosis research.

Material and methods: The human HSC cell line LX-2 was utilized to investigate the role of Meox1 in HSC activation. Fibrotic gene expression was analyzed, and assays were conducted to assess cell proliferation, migration and the cell cycle.

Results: Meox1 was identified as a positive regulator of HSC activation. We found that transforming growth factor-β1 (TGF-β1) treatment significantly upregulated Meox1 expression in a dose-dependent manner in LX-2 cells, and the expression levels of α-smooth muscle actin (α-SMA), collagen type I (collagen-I) and matrix metalloproteinase-2 (MMP-2) also increased progressively with higher concentrations of TGF-β1. Knockdown of Meox1 via small interfering RNA (siRNA) inhibited TGF-β1-induced expression of HSC activation markers and fibrotic genes, including α-SMA, collagen-I and MMP-2. Conversely, Meox1 overexpression promoted HSC activation, evidenced by increased levels of α-SMA, collagen-I and MMP-2. Meanwhile, Meox1 overexpression accelerated cell proliferation and enhanced cell migration. Additionally, forced expression of Meox1 in LX-2 cells elevated Smad3 phosphorylation level, although TGF-β1 and total Smad3 protein levels remained unchanged. Furthermore, we observed that Meox1 could induce a redistribution of the cell population, extending the G1 phase, and that Meox1-upregulated p21CIP1/WAF1 expression in LX-2 cells was independent of p53.

Conclusions: Our findings suggest that Meox1 plays a pivotal role in HSC activation and may be involved in the canonical TGF-β1/Smad pathway.

Background: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is implicated in various cancers, but its role in modulating ferroptosis and tumor cell behavior in non-small cell lung cancer (NSCLC) remains unclear.

Objectives: This study aimed to investigate how IGF2BP2-mediated N6-methyladenosine (m6A) modification of solute carrier family 7 member 11 (SLC7A11) affects ferroptosis and NSCLC cell viability.

Material and methods: NSCLC H1299 cells were transfected with either IGF2BP2 or SLC7A11 plasmids and corresponding siRNAs. Expression levels of IGF2BP2, SLC7A11 and ferroptosis markers were analyzed using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) and lipid peroxidation levels were measured with flow cytometry and biochemical kits. The RNA immunoprecipitation (RIP) and mRNA stability assays were utilized to explore the interaction between IGF2BP2 and SLC7A11.

Results: IGF2BP2 expression was significantly upregulated in H1299 cells. Overexpression of IGF2BP2 enhanced cell viability and decreased ferroptosis, whereas its knockdown resulted in reduced cell viability and increased ferroptotic activity. IGF2BP2 enhanced SLC7A11 mRNA stability through m6A modification, and SLC7A11 overexpression reversed the effects of IGF2BP2 knockdown. This interaction increased cell viability and reduced ROS and lipid peroxidation.

Conclusions: IGF2BP2 plays a critical role in NSCLC by stabilizing SLC7A11 mRNA via m6A modification, promoting cell proliferation and suppressing ferroptosis. Targeting the IGF2BP2-SLC7A11 axis may offer a promising therapeutic strategy for NSCLC.