Advances in Clinical and Experimental Medicine最新文献

Adverse childhood experiences (ACEs), such as childhood abuse and neglect, have a profound impact on our bodies, affecting the brain, autonomic nervous system, endocrine system, immune and inflammatory systems, as well as genetic expressions. Childhood maltreatment can leave long-lasting neurobiological scars, significantly increasing the risk of developing both physical and mental disorders, including depression and posttraumatic stress disorder (PTSD). The ICD-11, an international disease classification system, has recently introduced new diagnostic criteria for what is known as complex PTSD. In this context, we will briefly overview the neurobiological effects of ACEs, the associated health conditions they can lead to, and potential pathways to recovery. These pathways include promoting the reinstatement of emotional and interpersonal skills that may have been impaired during early development. Approaching ACEs from a holistic perspective may open new avenues for more effective clinical practices for individuals suffering both physically and mentally.

Background: With the increasing number of older pregnant women and environmental pollution, the incidence of congenital malformations increases every year. Prenatal diagnosis is an effective means of identifying congenital malformations.

Objectives: To evaluate the clinical utility of single nucleotide polymorphism (SNP) microarray analysis during prenatal evaluations.

Material and methods: To assess the similarities and differences between the 2 approaches, 425 pregnant women were selected to undergo prenatal gene SNP microarray analysis and karyotype analysis during prenatal evaluation between January 2020 and August 2021.

Results: The success rate of SNP microarray analysis was 100%, which was statistically different from that of karyotype analysis (92%, Fisher's exact test, p < 0.001). The positive rate of SNP detection was 10.4% higher than karyotype analysis, which was 6.6% (Pearson's χ2 test, χ2 = 3.89, degrees of freedom (df) = 1, p = 0.049). Karyotype analysis detected 28 cases of aneuploidy; SNPs could not only detect these results of karyotype analysis, but 16 cases of copy number variations (CNV) with obvious pathogenicity, including duplications/deletions, chimerism and loss of heterozygosity (LOH).

Conclusions: Single nucleotide polymorphism microarray analysis technology is an important method used in prenatal genetic evaluations, which can find fetal genetic etiologies, correctly evaluate the fetal prognosis during prenatal clinical examination, and provide a more objective basis for whether to continue the pregnancy.

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.

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: 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.

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.

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: 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.