Annals of medicine最新文献

Background: To validate the clinical efficacy of non-invasive prenatal diagnosis (NIPD) for spinal muscular atrophy (SMA) in the first trimester and extend its applicability to families without probands.

Method: From December 2020 to October 2024, 288 high-risk pregnancies were recruited prospectively, with 81 qualifying for NIPD after genetic counseling. Among the eligible cases, parent-based haplotypes were successfully constructed in 75 families (92.6%), while grandparent-based haplotype reconstruction was performed for the remaining 6 cases (7.4%) where proband samples were unavailable. Through targeted sequencing of the SMN1/SMN2 gene and flanking informative SNPs in maternal plasma, fetal haplotypes were inferred by analyzing dosage changes in cell-free DNA (cfDNA) using Bayes factor. All NIPD results were subsequently validated through invasive diagnostic procedures (chorionic villus sampling or amniocentesis).

Results: The haplotypes were successfully constructed in 81 families through parents or grandparents of the identified variant carriers. 76 families (93.8%) successfully obtained NIPD results, among which the earliest gestational week for successful NIPD was 7⁺³weeks, with a minimum fetal fraction of 1.9%. 5 cases were classified 'no call' results due to pathogenic variant-adjacent recombination events (2/5), insufficient or unevenly distributed informative SNPs (2/5), and subthreshold fetal fraction (1/5). The average gestational age of NIPD blood drawing is 9 weeks. Validation test showed the NIPD results accuracy was 100%.

Conclusion: This study demonstrates the clinical feasibility of grandparent-assisted haplotype construction for SMA families without probands and enables accurate early prenatal diagnosis of SMA in first-trimester pregnancies.

Background: Disease stability is an achievable goal in chronic obstructive pulmonary disease (COPD) management. However, the clinical implications of disease stability in patients with COPD remain unclear.

Methods: We conducted a single-center retrospective cohort study using the electronic medical records of treated patients with symptomatic COPD. Patients who had newly initiated inhaler therapy with long-acting β2-agonist/long-acting muscarinic antagonist (LABA/LAMA) or inhaled corticosteroid/LABA/LAMA combinations were included. Disease stability was defined over a one-year assessment period as meeting all of the following criteria: (1) symptom stability; (2) no moderate or severe exacerbations; and (3) no rapid decline in lung function. The outcomes included acute exacerbations and all-cause mortality.

Results: Of the 725 screened patients, 405 were eligible for inclusion in the study. Among them, 158 (39.0%) achieved disease stability. The proportions of patients who met each criterion were 70.4% for symptom stability, 63.7% for no exacerbations, and 71.4% for a non-rapid lung function decline. Only 5.9% met none of these criteria. During the follow up duration of median 62 (interquartile ranges, 30-90) months, disease stability was significantly associated with a reduced risk of moderate-to-severe (adjusted hazard ratio [aHR] 0.521, 95% confidence interval [CI] 0.392-0.692) and severe (aHR 0.393, 95% CI 0.279-0.553) exacerbations after adjusting for confounders. It was also associated with a decreased mortality risk (aHR 0.345, 95% CI 0.135-0.883).

Conclusion: Disease stability was associated with a lower risk of exacerbation and mortality, suggesting its potential role as a treatment target and outcome measure for COPD.

Background: Pathogenic autoantibody subclass switch has been found in lots of autoimmune disease. However, the information on anti-phospholipase A2 receptor antibody subclass switch in membranous nephropathy (MN) is limited and controversial. Here, we aim to uncover the subclass change during the PLA2R-associated MN progression.

Methods: Biopsy-proven PLA2R-associated MN cases with sufficient tissue for light microscopy, immunofluorescence, and electron microscopy (October 2022 - March 2023) were included. Serum levels of PLA2R-IgG4 and PLA2R-IgG were measured by TRFIA. The correlation of the ratio with EM stage and other clinical parameters was analyzed.

Results: Among 116 enrolled patients, glomerular IgG1 (r = 0.15, p = .01; r = 0.18, p = .002) and IgG3 (r = 0.17, p = .005; r = 0.27, p < .001) intensities were positively correlated with C3 and C1q intensities, respectively. The PLA2R-IgG4/PLA2R-IgG ratio was significantly positively correlated with serum albumin (r = 0.26, p = .005) but inversely correlated with both the intensity of glomerular IgG1 (r = -0.20, p = .03) and IgG3 deposits (r = -0.24, p = .009), as well as with C1q staining intensity (r = -0.27, p = .004). The median PLA2R-IgG4/PLA2R-IgG ratio significantly increased with pathological stage (Stage I: 18.92%; Stage II: 39.74%; Stage III: 59.38%; Stage IV: 68.99%) and was strongly positively correlated with EM stage (r = 0.52, p < .001). Advanced EM stages were observed more frequently with higher PLA2R-IgG4/PLA2R-IgG ratio.

Conclusions: During the disease progression, EM stages were correlated with altered autoantibody IgG subclass profiles: early stages featured IgG1 or IgG3 autoantibodies, while late EM stages shifted to IgG4 predominance.

Background: Transbronchial cryobiopsy (TBCB) is a minimally invasive technique that yields larger specimens than conventional transbronchial forceps biopsies (TBFB) and demonstrates superior diagnostic rates for interstitial lung diseases. However, the efficacy of TBCB compared to TBFB in evaluating peripheral pulmonary lesions (PPLs) is not well established. This study aims to examine the diagnostic performance of TBCB relative to TBFB in PPLs.

Material and methods: Between May 2021 and December 2023, patients with PPLs were enrolled and underwent TBFB followed by TBCB. These procedures were performed either in a hybrid operating room (HOR) or a standard bronchoscopy room without fluoroscopy. The study compared histopathology diagnostic yield between the two methods.

Results: The study included 84 patients. The median lesion size was 37 mm (interquartile range: 26, 54), with 16 lesions (19.0%) measuring less than 2.0 cm. Among the participants, 44 (52.4%) were diagnosed with lung cancer, and 28 (33.3%) had infectious diseases. TBCB yielded significantly larger tissue samples [60 mm³ (range: 30, 144) vs. 4 mm³ (range: 2, 6), p < 0.001] and higher diagnostic yields (94.0% vs. 77.1%, p < 0.001) than TBFB. The higher diagnostic yield for TBCB were consistent in both the bronchoscopic room (97.2% vs. 77.8%, p = 0.008) and HOR (91.5% vs. 76.6%, p = 0.033). The incidence of ≥ grade 3 bleeding was 7.1%.

Conclusion: TBCB significantly improves the diagnostic yield for PPLs, irrespective of fluoroscopic guidance, and is effective for both malignant and benign lesions. Furthermore, it is associated with minimal complications, affirming its safety and efficacy as a diagnostic procedure.HighlightsTBCB consistently provided a higher pathological yield compared to TBFB, independent of lesion size, use of fluoroscopy, or the nature of the pathology (benign or malignant)TBCB yielded larger tissue sample and had high successful rates for NGS testing.Combination of an ultrathin bronchoscope, augmented fluoroscopy, ROSE, and TBCB can lead to high diagnostic yields.

Background: Cough hypersensitivity syndrome (CHS) is a characteristic of patients with chronic cough (CC). Sensitive skin syndrome (SSS), which is characterised by cutaneous pain and pruritus, may share neural hypersensitivity mechanisms with CHS. This study aimed to determine the co-morbidities, clinical profiles, and psychosomatic correlates in CC patients.

Methods: Two hundred CC patients were enrolled in this prospective cohort study. SSS was diagnosed according to established guidelines, which required the presence of subjective symptoms induced by minimal stimuli with at least one of the following positive criteria: Sensitive Scale-10 score > 13; Sensitive Scale-14 score > 18; lactic acid sting test score ≥ 3; or capsaicin test score ≥ 3. Assessments included cough severity, Visual Analogue Scale (VAS), capsaicin cough sensitivity, cough symptom score, Leicester cough questionnaire (LCQ), and psychological evaluations.

Results: Among CC patients, 44.5% (89/200) had SSS with a higher prevalence in refractory/unexplained CC (RU-CC) patients compared to non-RU-CC patients (63.24% vs. 34.85%; p < 0.001). SSS patients exhibited heightened cough sensitivity (lower C2/C5 thresholds; p = 0.017/0.004), higher VAS scores (p = 0.026), lower LCQ scores, and an elevated psychological burden compared to non-SSS patients. In addition, RU-CC patients with SSS had superior cough responses to neuromodulators than non-SSS patients (LCQ improvement: 2.59 ± 2.36 vs. 1.26 ± 2.53; p = 0.037; response rate: 79.3% vs. 44.4%; p = 0.029).

Conclusion: SSS was identified in a clinically relevant subset of CC patients (especially those with RU-CC) and correlated with neural hypersensitivity and psychological distress. Early recognition of SSS in patients with CC and the early introduction of neuromodulators may offer greater therapeutic benefits and improve patient outcomes.

Background: The 2022 European Leukemia Net (ELN) risk stratification categorizes acute myeloid leukemia (AML) with myelodysplasia-related gene (MRG) mutations - including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and/or ZRSR2 - as "adverse-risk". However, the prognostic relevance of MRG mutations in patients with favorable-risk AML remains uncertain.

Methods: In this study, we analyzed a cohort of 221 adult patients with de novo favorable-risk AML. Risk groups were classified according to the 2022 European Leukemia Net guideline.

Results: A total of 47 AML patients (21.3%) harbored MRG mutations. The presence of MRG mutations was associated with older age (57 vs. 49, p = 0.005), lower white blood cell count (6.9 vs. 14.5, p = 0.015), and the presence of TET2 (27.7% vs. 10.9%, p = 0.004), MPL (6.4% vs. 0.6%, p = 0.031), and ETV6 (6.4% vs. 1.1%, p = 0.066) mutations. Our findings indicated that the presence of MRG mutations did not significantly impact 2-year overall survival (OS) (75.2% vs. 69.4%, p = 0.285) or leukemia-free survival (LFS) (58.9% vs. 52.5%, p = 0.640). However, patients with two or more MRG mutations had significantly poorer LFS than those with one MRG mutation (p = 0.004) or without MRG mutations (p = 0.001). By multivariable analysis, ≥2 MRG mutations was independently associated with worse LFS.

Conclusion: The presence of a single MRG mutation did not confer a worse prognosis in favorable-risk AML, whereas a high MRG mutation burden (≥2 mutations) was independently associated with poorer LFS. This study suggests that quantifying the MRG mutation burden may inform risk stratification in this patient population.

Background: Plant-derived exosome like nanovesicles known for their biocompatibility, minimal immunogenicity, and capacity to transport diverse therapeutic molecules, have emerged as effective carriers for targeted drug delivery. When integrated into hydrogels, these offer improved stability, prolonged release, and precise delivery to specific skin layers, thereby enhancing treatment outcomes.

Methods: We conducted structured search of the literature on plant-derived exosome-like nanovesicles (PDELNs) and hydrogel-based drug-delivery systems for skin applications. Relevant studies were identified from PubMed, ScienceDirect, and Google Scholar using keywords including plant-derived exosomes like nanovesicles, plant exosomes + skin, and plant exosomes + hydrogel. We selected Publications from 2010 to 2025 and focused on studies describing biological activity of plant-derived exosomes, as well as their therapeutic relevance for skin repair, regeneration, or wound healing. Research involving hydrogel formulations that incorporated plant-derived vesicles or comparable nano-carriers was also included. In vitro, in vivo (preclinical), and available clinical evidence were reviewed, while unrelated work (such as mammalian exosomes or non-skin studies) was excluded.

Results: The combination of plant-derived exosomes like nanovesicles and hydrogels is potential therapeutic candidate in addressing various skin disorders, including inflammatory diseases, wound healing, and skin regeneration. However, challenges remain, including the scalability of exosome production, stability of formulations, and achieving effective skin penetration. Furthermore, regulatory considerations regarding the safety, toxicity, and long-term biocompatibility of these systems must be thoroughly evaluated. The review also emphasizes future research opportunities, the development of plant-derived exosomes like nanovesicles with higher therapeutic potential and the integration of advanced technologies like phototherapy and microneedles to further improve therapeutic efficacy.

Conclusion: The combination of PDELNs with hydrogel delivery systems have shown potential in preclinical models for the treatment of dermatological diseases, providing a novel strategy for skin care.

Background: Growth factors (GFs), as key molecules regulating cellular processes, demonstrate therapeutic potential in fields such as regenerative medicine, oncology, and metabolic regulation. However, inherent pharmacokinetic limitations, off-target effects, and safety concerns significantly hinder clinical translation. Although in-depth studies on mechanisms of action, smart delivery systems, and regulatory networks have improved GFs' stability, targeting, and safety - leading to clinical approvals of some related drugs - high costs, complex large-scale production processes, and the intricacy of the in vivo microenvironment continue to restrict the scope and breadth of GFs' clinical translation.

Discussion: This review systematically examines the classification and fundamental research progress of GFs, emphasizing their current applications in neurodegenerative diseases, bone regeneration, and metabolic disorders. It thoroughly analyzes major challenges in clinical translation, including suboptimal pharmacokinetic properties, difficulties in precise delivery, potential side effects, and high industrial production costs. To address these bottlenecks, the paper summarizes corresponding solutions, such as structural optimization through protein engineering and chemical modification, development of smart responsive delivery systems (e.g. extracellular vesicle-based platforms), and utilization of multi-factor sequential release technologies to mimic physiological repair processes.

Conclusion: By synthesizing current advances and existing constraints, this study aims to provide a comprehensive roadmap and technical reference for accelerating the development of next-generation GF therapies. Future research should focus on developing scalable delivery platforms, reducing production costs through synthetic biology, and strengthening biomarker-based translational studies. Multidisciplinary integration holds promise for advancing GFs therapies towards greater precision, safety, and efficacy, positioning them as core therapeutic tools in the era of precision medicine for addressing degenerative diseases, tissue damage, and metabolic disorders.

Background: Clear-cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer, has limited treatment options. This study investigated the expression and clinical significance of DOCK4 in ccRCC, hypothesizing that DOCK4 could serve as a prognostic biomarker and correlate with the tumor immune microenvironment (TIME) and immunotherapy response.

Methods: We comprehensively analyzed data on DOCK4 expression levels and prognostic outcomes in ccRCC patients derived from tissue microarray (75 pairs) and the dataset (532 cases). Based on univariate and multivariate Cox regression analyses, we constructed a prognostic nomogram and validated its predictive accuracy and risk stratification ability using calibration curves and Kaplan‑Meier survival analysis. Immune cell infiltration analysis was conducted to investigate DOCK4's role in the TIME.

Results: Analysis of DOCK4 expression in ccRCC tissues revealed its notable overexpression. High DOCK4 expression was associated with more favorable pathologic staging and improved survival outcomes. DOCK4 shows high discriminatory power between tumor and normal samples, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.819. This association was confirmed using tissue microarray analysis. Further investigation indicated that high DOCK4 expression may play a crucial role in modulating the TIME, potentially enhancing susceptibility to immunotherapy and strengthening immune surveillance mechanisms.

Conclusions: DOCK4 is a promising prognostic biomarker in ccRCC, with high expression indicating favorable pathologic staging and improved survival. Its role in modulating the TIME suggests that DOCK4 could also serve as a therapeutic target, potentially guiding future immunotherapy strategies for this aggressive malignancy.