Annals of medicine最新文献

Insulin dependency arises from autoimmunity that targets the β cells of the pancreas, resulting in Type 1 diabetes (T1D). Despite the fact that T1D patients require insulin for survival, insulin does not provide a cure for this disease or prevent its complications. Despite extensive genetic, molecular, and cellular research on T1D over the years, the translation of this understanding into effective clinical therapies continues to pose a significant obstacle. It is therefore difficult to develop effective clinical treatment strategies without a thorough understanding of disease pathophysiology. Pancreatic tissue bioengineering models of human T1D offer a valuable approach to examining and controlling islet function while tackling various facets of the condition. And in recent years, due to advances in high-throughput omics analysis, the genotypic and molecular profiles of T1D have become finer tuned. The present article will examine recent progress in these areas, along with their utilization and constraints in the realm of T1D.

Background: Frailty is a common geriatric syndrome associated with poor clinical outcomes. Effectiveness of lifestyle intervention programmes among frail older people has been examined earlier, but effects of interventions on prevention of frailty have been rarely studied. The aim of this study was to investigate to what extent the multidomain lifestyle intervention in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) affected changes in frailty status among older men and women at risk of cognitive disorders.

Methods: The 2-year multidomain lifestyle intervention trial including simultaneous nutritional counseling, physical exercise, cognitive training and social activity, and management of metabolic and vascular risk factors, was conducted among 1259 older people (mean age 68.9 years). A modified Fried's frailty phenotype (weight loss, exhaustion, weakness, slowness, and low physical activity) was used to assess frailty at baseline and after the 2-year intervention. Participants with one or more components of the frailty phenotype were classified as pre-frail or frail. A multinomial regression model was applied to investigate efficacy of the intervention on frailty.

Results: We observed a favorable trend in reversing frailty among older men with the intervention. Pre-frail or frail men in the intervention group had higher probability of being non-frail after the intervention (44%) than pre-frail or frail men in the control group (30%) (p = 0.040). Among men, the intervention was especially beneficial in terms of increasing physical activity. Among women, multidomain lifestyle intervention did not affect the frailty status.

Conclusion: Modifying lifestyle-related factors may have potential to reverse first signs of frailty among older men. However, the intervention lasted only two years, therefore, research with longer follow-up is needed to see possible long-term effects of lifestyle management on the development of frailty.

Background: Intracranial aneurysms (IAs) are a significant clinical concern, with detection rates increasing due to advances in imaging technologies. However, precise mechanisms underlying their pathophysiology remain incompletely understood. Recent evidence suggests a pivotal role of oral microbiota dysbiosis, particularly periodontal pathogens, in systemic inflammation that may contribute to IA development and rupture.

Objective: This review aims to critically evaluate the association between oral microbiota dysbiosis and the pathogenesis of IAs, with a focus on the molecular and immunological mechanisms by which oral pathogens influence vascular pathology.

Methods: We conducted a comprehensive analysis of the literature regarding the impact of oral microbial dysbiosis on IA pathophysiology, emphasizing the role of specific pathogenic species, such as Porphyromonas gingivalis. The review explores how these pathogens may mediate chronic inflammation through hematogenous spread, gut microbiome alterations, and neuroinflammatory processes, leading to vascular remodeling and cerebrovascular instability.

Results: The findings suggest that oral microbial dysbiosis, particularly the presence of pathogenic bacteria, is implicated in the systemic inflammatory response that exacerbates the structural integrity of the cerebrovascular wall. Chronic inflammatory states induced by oral pathogens contribute to extracellular matrix degradation, impaired vascular remodeling, and an increased susceptibility to IA rupture.

Conclusions: The findings highlight the importance of maintaining oral microbiota homeostasis as a potential therapeutic target for preventing IAs. Interventions aimed at restoring oral microbial balance may represent a novel strategy for reducing the burden of IA formation and rupture, highlighting the need for an integrated approach to oral health and IAs prevention.

Objective: To explore the differences of conventional ultrasound characteristics, elastic imaging parameters and clinicopathological characteristics of distinct molecular subtypes of breast cancer in young women, and to identify imaging parameters that exhibited significant associations with each molecular subtype.

Methods: We performed a retrospective analysis encompassing 310 young women with breast cancer. Observations were made regarding the ultrasonography and elastography characteristics of the identified breast lesions. Subsequently, based on immunohistochemistry results patients were classified into five distinct molecular subtypes: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+, and triple-negative breast cancer (TNBC). Clinical, pathological, and ultrasound imaging features were compared among these subtypes using binary logistic regression analysis.

Results: Statistically significant differences were observed in various parameters across the five molecular subtypes (p < 0.05), including tumor size, morphology, margins, calcification, posterior echo features, blood flow (Adler grading), and tumor hardness. Specifically, luminal A subtype exhibited propensity for spiculated margins, lower blood flow grading, and decreased hardness; luminal B subtype was characterized by angular margins; HER2+ subtype manifested higher blood flow grading, calcification, and elevated hardness. Conversely, TNBC subtype displayed smooth margins, absence of calcification, and heightened hardness.

Conclusion: Specific molecular subtypes of breast cancer have unique ultrasonic and elastic imaging characteristics.

Background: The management of high-risk acute myeloid leukaemia (AML) remains challenging, highlighting the need for innovative conditioning strategies beyond current regimens.

Methods: In the present single-arm study, a FACT regimen comprised of low-dose total body irradiation (TBI) with fludarabine, cytarabine and cyclophosphamide was employed to treat cytogenetically high-risk AML patients exhibiting pre-transplant active disease. This clinical trial is registered in the Chinese Clinical Trial Registry with the registration number ChiCTR2000035111.

Results: In this study, 21 high-risk AML patients with pre-transplant disease statuses including primary induction failure, relapse and measurable residual disease positivity, were enrolled to undergo FACT conditioning. The FACT group demonstrated a 1-year non-relapse mortality (NRM) rate of 9.5%, indicating a similar level of safety and tolerability among the conditioning regimens. The estimated cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) at one year was 30.7%. Additionally, the cumulative incidence of chronic GVHD was 36.0% at one year and increased to 43.0% at two years.

Conclusions: The FACT regimen is an effective myeloablative conditioning (MAC) strategy for high-risk AML patients, potentially reducing relapse risk without increasing NRM, warranting further research.

Background: Cord blood (CB) is widely used in treating haematologic disorders due to its broad availability, tolerance to significant histocompatibility antigen disparities, and low incidence of chronic graft-versus-host disease (cGVHD). The cord blood transplantation (CBT) with anti-thymocyte globulin (ATG)-containing conditioning regimens shows promise in this regard.

Methods: We conducted a retrospective review of data from patients who underwent CBT at our centre from August 2003 to December 2022. Patients undergoing CBT with ATG were matched with those who received HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Propensity score matching (PSM) was utilized to form 105 matched pairs (140 patients) for comprehensive trial analysis.

Results: The cumulative incidence of neutrophil and platelet engraftment was significantly lower in the CBT group. Patients in the CBT group exhibited significantly lower incidences of grade II-IV acute GVHD (aGVHD) and cGVHD compared to the haplo-HSCT group (8.57% vs. 29.52%, p = 0.012; 20% vs. 39.05%, p = 0.031). The overall survival (OS) rate for the CBT and haplo-HSCT groups showed no significant difference. In patients with leukaemia, the CBT cohort showed better OS, GVHD-free and relapse-free survival (GRFS), as well as a lower incidence of disease relapse, although there was no statistical difference.

Conclusion: Our single-centre retrospective long-term follow-up investigations indicated that although the implantation rate of CBT is lower than that of haplo-HSCT, patients undergoing CBT with ATG-containing conditioning regimens may have a comparable overall survival with a lower risk of GVHD compared to those undergoing haplo-HSCT.

Objectives: The aim of the study was to evaluate the detection rate of genetic abnormalities in cases of foetal gallbladder (FGB) size abnormalities to determine whether these abnormalities justify prenatal diagnosis.

Methods: Two hundred and twenty-seven foetuses with gallbladder (GB) size anomalies who underwent prenatal diagnosis between January 2015 and June 2024 were included in the study. All these patients underwent chromosomal microarray and/or karyotyping, and 37 cases also underwent whole exome sequencing (WES). Two hundred and eight cases were followed up for postnatal outcomes. Then, we reviewed the literature of FGB anomalies cases with confirmed chromosomal results.

Results: The study included 227 foetuses, comprising 60 cases with isolated GB size anomalies and 167 cases with non-isolated GB size anomalies. Non-isolated GB size anomalies were associated with findings such as hyperechogenic bowel, ventriculomegaly, foetal growth restriction (FGR), cardiac anomalies, renal dysplasia and single umbilical artery. The overall diagnostic yield of genetic tests was 10.57% (24/227). Aneuploidies were identified in seven foetuses. Pathogenic/likely pathogenic copy number variations (CNVs) were found in nine foetuses, and α0-thalassemia in five foetuses. Additionally, three pathogenic single-nucleotide variants (SNVs) were detected through WES. Foetuses with non-isolated GB size anomalies showed a higher rate of detecting genetic abnormalities compared to those with isolated GB size anomalies, with a significant difference in statistical analysis (13.2% vs. 3.3%, p = .033, Chi-square test). A total of eight studies, involving 407 cases met the criteria for inclusion in the systematic review. Overall, 28 foetuses were identified to have chromosomal abnormalities (6.9%, 28/407).

Conclusions: This study indicates that parents of foetuses with GB size anomalies should be informed about the potential for aneuploidy, pathogenic CNVs and SNVs, and genetic testing should be recommended in cases of non-isolated foetal GB size anomalies.

Purpose: To evaluate levels of 3 tear-soluble neuropeptides in dry eye patients and to identify the correlations with clinical signs and symptoms.

Methods: A total of 16 dry eye patients and 12 healthy volunteers were enrolled. Dry eye disease (DED) diagnosis was based on the 2017 Report of the Tear Film & Ocular Surface Society International Dry Eye Workshop (TFOS DEWS II). First time of noninvasive breakup time (NIBUT-1st), mean time of noninvasive breakup time (NIBUT-avg), tear meniscus height (TMH), Schirmer test, corneal fluorescein staining (CFS) score and ocular surface disease index (OSDI) were recorded. Tear fluid samples were collected and enzyme-linked immunoassay (ELISA was performed to analyze levels of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and substance P (SP), as well as the association among the 3 neuropeptides and clinical findings.

Results: Compared to normal controls, levels of tear CGRP (p=.003) and SP (p=.002) were significantly decreased in dry eye patients yet not NPY concentrations. Levels of tear CGRP and SP showed an inverse correlation with CFS and OSDI, which positively correlated with NIBUT-1st, NIBUT-avg and Schirmer test values. Multiple linear regression analysis showed that Schirmer test values were related to tear CGRP concentration. Subgroup analysis showed lower tear CGRP concentration in DED patients with severe symptoms (OSDI ≥ 46).

Conclusions: Levels of tear CGRP and SP decreased in DED patients and showed meaningful correlations with clinical symptoms and signs, implying a potential relationship between tear neuropeptides and ocular neurosensory function.

Background: The oral microbiota is a diverse and complex community that maintains a delicate balance. When this balance is disturbed, it can lead to acute and chronic infectious diseases such as dental caries and periodontitis, significantly affecting people's quality of life. Developing a new antimicrobial strategy to deal with the increasing microbial variability and resistance is important. Cold atmospheric plasma (CAP), as the fourth state of matter, has gradually become a hot topic in the field of biomedicine due to its good antibacterial, anti-inflammatory, and anti-tumor capabilities. It is expected to become a major asset in the regulation of oral microbiota.

Methods: We conducted a search in PubMed, Medline, and Wiley databases, focusing on studies related to CAP and oral pathogenic microorganisms. We explored the biological effects of CAP and summarized the antimicrobial mechanisms behind it.

Results: Numerous articles have shown that CAP has a potent antimicrobial effect against common oral pathogens, including bacteria, fungi, and viruses, primarily due to the synergy of various factors, especially reactive oxygen and nitrogen species.

Conclusions: CAP is effective against various oral pathogenic microorganisms, and it is anticipated to offer a new approach to treating oral infectious diseases. The future objective is to precisely adjust the parameters of CAP to ensure safety and efficacy, and subsequently develop a comprehensive CAP treatment protocol. Achieving this objective is crucial for the clinical application of CAP, and further research is necessary.

Angiogenesis is a complex physiological process. In recent years, the immune regulation of angiogenesis has received increasing attention, and innate immune cells, which are centred on macrophages, are thought to play important roles in vascular neogenesis and development. Various innate immune cells can act on the vasculature through a variety of mechanisms, with commonalities as well as differences and synergistic effects, which are crucial for the progression of vascular lesions. In recent years, monotherapy with antiangiogenic drugs has encountered therapeutic bottlenecks because of the short-term effect of 'vascular normalization'. The combination treatment of antiangiogenic therapy and immunotherapy breaks the traditional treatment pattern. While it has a remarkable curative effect and survival benefits, it also faces many challenges. This review focuses on innate immune cells and mainly introduces the regulatory mechanisms of monocytes, macrophages, natural killer (NK) cells, dendritic cells (DCs) and neutrophils in vascular lesions. The purpose of this paper was to elucidate the underlying mechanisms of angiogenesis and development and the current research status of innate immune cells in regulating vascular lesions in different states. This review provides a theoretical basis for addressing aberrant angiogenesis in disease processes or finding new antiangiogenic immune targets in inflammation and tumor.