Annals of medicine最新文献

Background: Maternal colonization with Group B Streptococcus (GBS) disrupts the vaginal microbiota, potentially affecting infant microbiota assembly and growth. While the gut microbiota's importance in infant growth is recognized, the specific effects of maternal GBS on growth remain unclear. This study aimed to explore the effects of maternal vaginal GBS during pregnancy on early infant growth, microbiome, and metabolomics.

Methods: We recruited and classified 453 pregnant women from southern China into GBS or healthy groups based on GBS vaginal colonization. Their infants were categorized as GBS-exposed or GBS-unexposed groups. We comprehensively analyzed infant growth, gut microbiota, and metabolites during early life, along with maternal vaginal microbiota during pregnancy, using 16S rDNA sequencing and targeted metabolomics.

Results: GBS-exposed infants exhibited lower length-for-age z-scores (LAZ) than GBS-unexposed infants, especially at 2 months. Altered gut microbiota and metabolites in GBS-exposed infants correlated with growth, mediating the impact of maternal GBS on infant LAZ. Changes in the vaginal microbiota of the GBS group during the third trimester correlated with infant LAZ. Additionally, differences in neonatal gut microbiota, metabolites, and vaginal microbiota during pregnancy were identified between infants with overall LAZ<-1 within 8 months after birth and their counterparts, enhancing the discriminatory power of fundamental data for predicting the occurrence of LAZ<-1 during the first 8 months of life.

Conclusions: GBS exposure is associated with decreased infant length growth, with altered microbiota and metabolites potentially mediating the effects of maternal GBS on offspring length growth, offering potential targets for predicting and addressing growth impairment.

Objective: Ruptured peripheral cerebral aneurysm (PPCA) associated with moyamoya disease (MMD) is rarely reported, and its optimal treatment remains controversial. This study aims to present the clinical characteristics, treatment strategies, and outcome predictors of this rare clinical entity.

Methods: A retrospective review of patients with hemorrhagic MMD from January 2013 to December 2020 was performed. All medical records were independently compiled and reviewed.

Results: Twenty-three patients were identified, 56.5% of whom were female. The mean age was 45.9 years with a peak age of onset of 51-60 years. Most patients (65.2%) developed intraventricular hemorrhage with or without intracerebral hemorrhage. These aneurysms were frequently located on the anterior (26.1%) and posterior (43.5%) choroidal arteries. Sixteen (69.6%) aneurysms were embolized and the remaining 7 (30.4%) were managed conservatively due to approach inaccessibility. Good outcomes were achieved in 82.6% of all cases, with 81.3% for embolization and 85.7% for observation. Complete occlusion was observed in all 16 aneurysms embolized. Of the conservatively treated aneurysms, 1 (14.3%) re-ruptured, 1 (14.3%) decreased in size, 2 (28.6%) disappeared, and 3 (42.8%) remained stable in size. Aneurysm rebleeding was associated with an unfavorable outcome (P = 0.026).

Conclusions: PPCA should be considered in the differential diagnosis of hemorrhagic MMD. Aneurysm rebleeding appears to be a potential predictor of poor outcome and therefore aggressive intervention should be advocated. Endovascular embolization may be safe and feasible, and conservative observation should be carefully chosen given the high risk of aneurysm re-rupture.

Objective: To investigate the optic disc changes (ODC) in Chinese patients with NLRP3-associated autoinflammatory disease (NLRP3-AID).

Methods: Patients who were diagnosed with NLRP3-AID at the Department of Rheumatology, Peking Union Medical College Hospital between April 2015 and December 2022 were retrospectively reviewed and analyzed.

Results: A total of 20 patients were enrolled in this retrospective study. All 20 patients had a moderate MWS NLRP3-AID phenotype. Thirteen patients (65%) had ocular involvements. The interval between symptoms onset and diagnosis was significantly longer in patients with ocular involvement than in patients without (p = 0.044). The incidence of hearing loss was significantly higher in patients with ocular involvement (p = 0.017), while the incidence of abdominal pain was significantly lower when compared to patients without ocular involvement (p = 0.007). Optic disc swelling (ODS) (50%) was the most common ODC. All of the four T348M mutation carriers within our cohort exhibited ODS with visual-field defects. There was a significant difference between patients with/without ODS regarding the number of patients carrying T348M mutation (p = 0.014). The occurrence of hearing loss and CNS involvement was significantly higher in the group with ODS compared to the group without (p = 0.0014, p = 0.0198). Of the eight patients who underwent lumbar puncture, five presented with intracranial hypertension (IH). ODS was observed in all patients with IH. The serum inflammatory markers were significantly higher in patients with ODS than in those without. Two patients receiving regular subcutaneous IL-1 inhibitor treatment showed improvements in ODC.

Conclusions: ODC is common among Chinese patients with NLRP3-AID, with ODS being the most common manifestation. Hearing loss and CNS involvement often accompany the occurrence of ODS. The serum inflammatory markers are associated with ODS. The T348M mutation is more likely to lead to ODC with visual-field defects.

Background: In recent years, daratumumab (DARA) has gained widespread use in the treatment of systemic light chain (AL) amyloidosis. In this study, we assessed the efficacy and safety of a DARA treatment strategy based on serum free light chain (sFLC) levels and non-fixed cycles.

Methods: The study included 123 patients with Al amyloidosis who received DARA at our center between July 2020 and September 2023. All patients received the standard DARA treatment (16 mg/kg weekly for four weeks) during the first course. Subsequent treatments were adjusted based on sFLC levels and the physician's judgment.

Results: The results demonstrated an impressive overall hematologic response rate (ORR) of 94.3%, with a hematologic very good partial response (VGPR) and complete response (CR) rate of 84.5%. Median time to best hematologic response was 1 months. Cardiac and renal response rates were 39.3% and 60.3%, respectively. Thirty patients experienced grade 1/2 infusion-related reactions after the first infusion. The rate of grade 3/4 adverse events was 21%. The most common adverse events of grade 3 or 4 were pulmonary infection (6.5%), neutropenia and lymphocytopenia (5.7%), elevated transaminases (1.6%), acute kidney injury (1.6%). After a median follow-up of 13 months (range 1-38), The 1-year OS and PFS estimates were 96.5% and 84.4%, respectively.

Conclusion: These findings indicate that the sFLC levels based and non-fixed cycle DARA strategy is an efficacious and safe treatment strategy in both newly diagnosed and relapsed/refractory AL amyloidosis.

Objective: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease (MDA5⁺DM-ILD) often leads to acute respiratory failure and endangers lives. This study quantitatively analysed chest high-resolution computed tomography (HRCT) images to assess MDA5⁺DM-ILD and establish a risk prediction model for severe ILD within six months.

Methods: We developed a 'Standardized Threshold Ratio Analysis & Distribution' (STRAD) to analyse lung HRCT images. In this retrospective study, 51 patients with MDA5⁺DM-ILD were included and divided into severe-ILD and non-severe-ILD groups based on the occurrence of acute respiratory failure within six months post-diagnosis of MDA5⁺DM. The STRAD parameters, clinical indicators and treatments were compared between the two groups. Least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal STRAD parameters. Multivariate analysis selected clinical factors to be further combined with STRAD to enhance the predictive performance of the final model (STRAD-Ro52 model).

Results: Significant differences were observed between the two groups in STRAD parameters, anti-Ro52 antibody titers, presence of anti-Ro52 antibodies, age, ESR, ALB, Pa/FiO₂, IgM and IL-4 levels. The STRAD parameters were significantly correlated with demographic, inflammatory, organ function and immunological indicators. Lasso logistic regression analysis identified the -699 to -650 HU lung tissue proportion (%V7) as the optimal parameter for predicting severe ILD and S6·%V7, and the distribution of %V7 in the mid lungs was the optimal space parameter. Multifactorial regression of clinical indicators showed that the presence of anti-Ro52 antibodies was an independent risk factor for severe ILD, leading to the establishment of the STRAD-Ro52 model.

Conclusions: The STRAD-Ro52 model assists in identifying MDA5⁺DM patients at risk of developing severe ILD within six months, further optimizing precise disease management and clinical research design.

Background: Congenital hypothyroidism (CH) is a common metabolic disorder in children that can impact growth and neurodevelopment, particularly during infancy and early childhood. DUOXA2, a DUOX maturation factor, plays a crucial role in the maturation and activation of dual oxidase DUOX2 (a member of the NADPH oxidase family). DUOX2 can correctly migrate to the plasma membrane from the endoplasmic reticulum (ER) with the help of DUOXA2, and the two proteins together form a stable complex that promotes hydrogen peroxide (H2O2) generation in the synthesis of thyroid hormones. Genetic alterations in DUOXA2 lead to defects function of DUOX2 protein causing inherited CH.

Objectives: This review discusses the relationship between DUOXA2 and CH, including the pathogenic mechanisms of CH in children caused by DUOXA2 mutations and the possibility or promise of DUOXA2 gene screening as a diagnostic marker for CH in the clinic.

Methods: The review synthesizes current research on the biological role of DUOXA2 and DUOX2 in thyroid hormone synthesis, the molecular impact of DUOXA2 mutations, and the clinical implications of genetic screening for CH.

Results: Mutations in DUOXA2 disrupt this process of H2O2 generation in the synthesis of thyroid hormones , leading to inherited CH. Early identification through DUOXA2 gene screening could improve diagnostic accuracy, which facilitates early intervention and personalized treatment.

Conclusions: DUOXA2 gene screening holds promise for enhancing diagnostic accuracy in CH. However, it cannot be used as a sole diagnostic indicator, and to optimize diagnostic sensitivity, it should be combined with the screening of other relevant genetic mutations and diagnostic tools. Further research is needed to refine screening protocols and explore therapeutic options.

Background: Adenovirus (ADV) pneumonia in children is a significant contributor to the occurrence of post-infectious bronchiolitis obliterans (BO). Heparin sodium has known anti-inflammatory, immunomodulatory, and tissue repair properties. However, its role in treating BO after ADV infection remains unclear.

Methods: A retrospective analysis was conducted on 793 children diagnosed with ADV pneumonia and hospitalized in the southern region from January 2019 to December 2019. Among them, 307 cases were classified as single ADV pneumonia. We utilized directed acyclic graphs to analyze the causal relationships between various variables, which further helped us identify the independent and confounding variables for constructing our regression model. Propensity score matching (PSM) was also employed to control for confounding variables that could not be intervened in this study, ensuring baseline level equilibrium and correction. We utilized univariate logistic regression analysis to explore the factors influencing BO development after ADV pneumonia.

Results: Among the 793 children diagnosed with ADV pneumonia, 86 cases (10.84%) progressed to BO. The proportion of heparin use was higher in the non-BO group than in the BO group after PSM. The univariate regression analysis revealed that acute respiratory failure, neurological involvement and fibrinogen (FIB) were risk factors for the development of BO in ADV pneumonia cases (OR > 1, p < 0.05), but low-dose heparin sodium treatment and hemoglobin (OR < 1, p < 0.05) exhibited protective effects against BO formation. Among the 307 children with single ADV pneumonia (excluding confounding factors), 33 cases (10.75%) developed BO. The univariate regression analysis further indicated that fever duration, acute respiratory failure and FIB were risk factors for the development of BO in single ADV pneumonia (OR > 1, p < 0.05), while low-dose heparin sodium treatment (OR < 1, p < 0.05) was protective against BO formation after a single ADV pneumonia.

Conclusion: Low-dose heparin sodium treatment may be a protective factor against the development of BO after ADV pneumonia infection.

Background: Despite high COVID-19 vaccine coverage in Canada, vaccine acceptance and preferred delivery among newcomers, racialized persons, and those who primarily speak minority languages are not well understood. This national study explores COVID-19 vaccine acceptance, access to vaccines, and delivery preferences among ethnoculturally diverse population groups.

Methods: We conducted two national cross-sectional surveys during the pandemic (Dec 2020 and Oct-Nov 2021). Binary logistic regression analysis investigated the association between newcomer, language, and racialized minority respondents' perceptions and acceptance of COVID-19 vaccines, experiences of discrimination when accessing health services, and sociodemographic characteristics. McNemar-Bowker tests were used to assess changes in responses collected at two time points.

Results: Among 1630 respondents, 30.8% arrived in Canada within the last five years, 87.4% self-identified as a racialized minority, and 37.2% primarily spoke languages other than English or French. Although single dose COVID-19 vaccine uptake was at 92.7% among respondents, 14.8% experienced difficulty accessing vaccines, citing a need for translated resources or multi-lingual personnel. In longitudinal analysis, respondents were increasingly motivated over time to overcome barriers to accessing vaccines (61.4% to 69.6%, p = <.001). Fifty-nine percent (59.9%) of respondents would accept annual vaccination and over half would accept co-administration with routine (56.2%) or influenza (52.3%) vaccines. Experiences of racism/discrimination upon health service access were reported by 12.3% of respondents, who recommended increasing culturally safe practices and community involvement at vaccination sites.

Conclusions: Understanding how newcomers, racialized peoples, and minority language speakers perceive and access COVID-19 vaccines will support vaccination campaigns to optimize equitable access.

Background: Substance use disorders are multifaceted conditions influenced by both genetic and environmental factors. Serotonergic pathways are known to be involved in substance use disorder susceptibility, with genetic markers within serotonin receptor genes identified as potential risk factors.

Methods: To further explore this relationship, we conducted a study to investigate the association between several polymorphisms in five serotonin receptor genes (HTR1B, HTR2A/B, HTR3A/B) and substance use disorders (SUD) in Jordanian males by sequencing genotypes in 496 SUD patients and 496 healthy controls.

Results: Our findings revealed an allelic association between rs9567735 in the HTR2A gene and rs17586428 in the HTR2B gene with SUD. Haplotype analysis also showed that one haplotype of the HTR2A gene and four haplotypes of the five included genes were significantly associated with SUD risk. Moreover, we found that motives for substance use were correlated with single nucleotide polymorphisms SNPs rs1923882 and rs1150226, with the latter SNP also being associated with smoking.

Conclusion: These findings suggest that genetic variants of human 5-HT receptor genes may affect individual susceptibility to SUD in Jordan. However, further studies with larger sample sizes and additional variants in the same or different genes must confirm these findings.

Objectives: To explore the effect and the probable mechanisms of JLD in the treatment of type 2 diabetes mellitus (T2DM) - associated cognitive impairment (TDACI).

Methods: The effect of JLD in combating TDACI was assessed in T2DM model mice by conducting Morris water maze (MWM) behaviour testing. Active components and their putative targets, as well as TDACI-related targets, were collected from public databases. Protein-protein interactions (PPIs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and molecular docking were then utilized to explore potential molecular network mechanisms. Finally, the main targets were verified in animal model experiments.

Results: MWM test showed that JLD improved aspects of behaviour in T2DM model mice. JLD improved glucose intolerance, tissue insulin sensitivity, lipid metabolism and enhanced synapse-associated protein expression in hippocampus tissue. Network pharmacology revealed 185 active components, 337 targets of JLD, and 7998 TDACI related targets were obtained . PPI network analyses revealed 39 core targets. GO and KEGG analyses suggested that JLD might improve TDACI by regulating gene expression, apoptotic processes and inflammatory responses mainly via PI3K-AKT and AGE-RAGE signaling pathways. Molecular docking revealed strong binding of the main components to core targets. JLD reduced hippocampus tissue expression of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL6), core targets of treatment of TDACI.

Conclusions: The findings suggested that JLD has the potential to improve TDACI through multiple components, multiple targets and multiple pathways. JLD may be a promising treatment for diabetic cognitive impairment.