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Mental disorders are significant contributors to the global disease burden, of which depression and anxiety are the most common mental disorders diseases. We aimed to achieve a more accurate representation of the health burden of depression and anxiety using the standardized Global Burden of Disease methodologies. To measure temporal patterns and evaluate trends in age-standardized rates of anxiety and depression, age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized disability-adjusted life years rate (ASDR) are calculated from 1990 to 2021. Temporal trends from 1990 to 2021 were strictly examined by using Joinpoint regression analysis to identify significant changes in trends over time. This methodological approach enabled the calculation of the annual percentage change, the average annual percentage change, and their respective 95% confidence intervals (CIs). The analyses were broken down by gender, 20 age groups, 21 Global Burden of Disease regions, 204 countries/territories, and 5 sociodemographic index (SDI) quintiles. Globally, from 1990 to 2021, ASPR, ASIR, and ASDR for anxiety in 2021 have increased by 0.63 (95% CI: 0.55-0.74), 0.69 (95% CI: 0.61-0.81), and 0.64 (95% CI: 0.55-0.74), respectively. For depression, corresponding increases were 0.36 (95% CI: 0.3-0.45), 0.49 (95% CI: 0.4-0.63), and 0.43 (95% CI: 0.35-0.54), respectively. Gender comparisons and geographical and demographic distribution showed notable differences in the 2 diseases burden. The specific manifestation is that females consistently showed higher burden than males for both disorders. High-SDI regions had the highest age-standardized rates for anxiety, whereas for depression, the highest rates were observed in low-SDI regions. From 1990 to 2021, ASPR, ASIR, and ASDR for anxiety and depression exhibited significant annual increases, particularly pronounced during the COVID-19 pandemic. Epidemiological trends during the period emphasize significant disparities in the burden of anxiety and depressive disorders across geographic, demographic, and socioeconomic dimensions. These findings underscore the urgent need for targeted mental health interventions, particularly in high-burden regions like Tropical Latin America and among females and younger populations, to address the rising burden of anxiety and depression.

Ankylosing spondylitis (AS) represents a significant global health challenge, characterized by progressive stiffness and rigidity of the axial skeleton and sacroiliac joints, which severely impact patients' daily activities. Despite the availability of various therapeutic options, a substantial proportion of AS patients remain inadequately managed, underscoring the urgent need for novel treatment strategies. This study aimed to identify potential therapeutic targets for AS by investigating the association between circulating plasma proteins and the risk of developing AS. We conducted a comprehensive protein-wide Mendelian randomization analysis to assess the potential causal relationship between plasma proteins and the risk of AS. Plasma protein data were sourced from the UK Biobank Pharma Proteomics Project, which encompasses genome-wide association study data for 2940 plasma proteins. Additionally, genome-wide association study data for spondylosis were obtained from the Finnish R9 database. Colocalization analysis was performed to identify shared causal variants between plasma proteins and AS. Our findings indicated that the predicted plasma levels of 4 proteins were positively associated with the risk of spondylosis (PFDR < .05). Among these 4 plasma proteins, colocalization analysis suggested that they share common variants with spondylosis (PPH3 + PPH4 > 0.5), highlighting their potential as direct therapeutic targets for intervention. This study explores the potential causal relationships between 4 plasma proteins and AS, contributing to the understanding of potential therapeutic targets for this condition.

Multiple sclerosis (MS) represents a significant global public health concern. Risk factors for MS include autoimmune diseases and immune cell dysfunctions. Immune cells, particularly T cells, B cells, and monocytes, play pivotal roles in the pathogenesis of MS. Nevertheless, the direct causal relationship between these immune cells and MS remains unclear. Genome-wide association studies (GWAS) and Mendelian randomization (MR) offer promising avenues for elucidating genetic susceptibilities and causal relationships between immune cell traits and MS risk. In this study, we employed a 2-sample MR approach to investigate the probable causal connection between immune cells and MS. Immune characteristics, including median fluorescence intensity, relative counts, absolute counts, and mean percentages, were determined using published GWAS data and public resources from the integrative epidemiology unit Open GWAS database. The primary analysis method for MR was inverse variance weighted. Additionally, sensitivity analyses were conducted to validate the robustness of our findings. In this study, we identified that 4 immune traits among 2 immune profiles (relative cell and median fluorescence intensity) demonstrated a significant causal association with MS, including CD27 on IgD- CD38dim B cell (PFDR = 2.81 × 10-3), CD27 on memory B cell (PFDR = .024), CD3 on human leukocyte antigen DR+ CD4+ T cell (PFDR = .031), and CD28 on CD28+ CD45RA+ CD8+ T cell (PFDR = .049). The reverse MR analysis showed that MS did not have significant effects on these immunophenotypes (P > .05). Sensitivity analyses confirmed the robustness of the results (P > .05). Our study has provided evidence indicating a causal relationship between immune cells and MS, which provided new ideas and therapeutic targets for the study of immune mechanism of MS.

Rationale: Noonan syndrome (NS) is a RASopathy most frequently associated with mutations in HRAS, NRAS, KRAS, and RRAS2. The contribution of MRAS variants to NS pathogenesis remains poorly characterized, and infective endocarditis (IE) is extremely rare in patients with NS.

Patient concerns: A 22-year-old woman presented with typical dysmorphic features of NS, including short stature, broad forehead, hypertelorism, low-set posteriorly rotated ears, and a broad neck. She developed fever and progressive exertional dyspnea.

Diagnoses: Echocardiography demonstrated obstructive hypertrophic cardiomyopathy with vegetation located in the left ventricular outflow tract. Blood cultures grew Streptococcus mutans. Whole-exome sequencing identified a heterozygous MRAS c.203C>T (p.Thr68Ile) mutation affecting a highly conserved residue among RASopathy-associated GTPases, supporting the diagnosis of MRAS-associated Noonan syndrome complicated by infective endocarditis.

Interventions: Antibiotic therapy was escalated to intravenous gentamicin (60 mg daily) combined with ceftriaxone in accordance with the 2023 European Society of Cardiology guidelines for infective endocarditis.

Outcomes: After one month of intravenous gentamicin and ceftriaxone therapy, fever resolved, and follow-up echocardiography showed disappearance of the vegetation. Residual cardiac abnormalities persisted, including marked left ventricular hypertrophy with left ventricular outflow tract obstruction, left atrial enlargement, moderate mitral regurgitation, patent foramen ovale with minor shunting, and impaired diastolic function. Exertional dyspnea remained despite resolution of the infection.

Lessons: This case expands the genotypic spectrum of Noonan syndrome by supporting MRAS mutations as pathogenic drivers. It also identifies infective endocarditis as a previously unreported complication in MRAS-associated NS with outflow tract obstruction, highlighting the importance of careful cardiac surveillance in patients with RASopathies.

Rationale: The awake prone position (APP) has been recognized for its efficacy in decreasing mortality rates among patients suffering from acute respiratory distress syndrome (ARDS). While APP is frequently employed in non-intubated ARDS patients, its utilization in individuals with lung adenocarcinoma to boost oxygenation is not widely documented.

Patient concerns and diagnoses: A 61-year-old male presented with a 2-month history of cough, sputum, dyspnea, and weight loss. Upon examination, his oxygen saturation was recorded at 80%, and auscultation indicated the presence of numerous moist rales in both pulmonary fields. Chest computed tomography (CT) revealed extensive ground-glass opacities, thickened septa, and right lower lobe consolidation. Bronchoscopy showed a substantial amount of clear, frothy sputum in both lungs; however, polymerase chain reaction analysis of the bronchoalveolar lavage fluid did not identify any microorganisms. A transbronchial lung biopsy confirmed the diagnosis of lung adenocarcinoma.

Interventions: Given the patient's deteriorating respiratory condition, it was determined to initiate prone ventilation. Remarkably, after 30 minutes of commencing prone ventilation, there was a significant improvement in his oxygenation levels. A subsequent reassessment of the lung CT after 2 days of treatment in the prone position demonstrated a reduction in lung lesions and an enhancement in ventilation compared to the initial presentation.

Outcomes: After 1 week of daily APP (12 hours/d), oxygenation improved sufficiently to avoid intubation. Following genetic testing results, targeted therapy with vemurafenib was started. The patient was discharged after 1 week of combined treatment. A 1-month follow-up CT demonstrated substantial resolution of pulmonary lesions.

Lessons: This case report details the management of a patient with lung adenocarcinoma complicated by acute respiratory failure, who underwent innovative awake prone positioning ventilation. After daily APP treatment for 12 hours over 1 week, significant improvement in oxygenation was observed, and tracheal intubation was successfully avoided. Following 1 week of combined treatment with the targeted drug vemurafenib, the patient was discharged without complications. A follow-up CT scan 1 month later revealed substantial resolution of the pulmonary lesions. Early use of the APP may be a potential treatment option for patients with respiratory failure from lung adenocarcinoma that may avoid progression to tracheal intubation.

Systemic inflammation is increasingly recognized as a critical factor in the development of coronary heart disease (CHD). The systemic inflammation response index (SIRI) integrates the neutrophil, lymphocyte, and monocyte counts to provide a comprehensive inflammatory marker. However, the relationship between the SIRI and CHD risk remains unclear. This study aimed to investigate the association between SIRI and CHD risk in adults using data from the 2012 to 2018 National Health and Nutrition Examination Survey (NHANES) 2012-2018. Restricted cubic spline (RCS) analysis was conducted to explore potential nonlinear relationships, and subgroup analyses were used to evaluate the demographic and clinical modifiers. Logistic regression analysis was performed to assess the association between SIRI and CHD risk after adjusting for demographic, behavioral, and clinical covariates. RCS analysis examined nonlinear trends and subgroup analyses stratified the results by age and sex. Of the 8612 participants initially screened, 1121 were included in the final analysis. Elevated SIRI levels were significantly associated with higher CHD risk (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.05-1.25, P < .001). RCS analysis showed a linear relationship between the SIRI and CHD risk (P for nonlinearity = .056). Subgroup analysis demonstrated stronger associations in males (OR = 1.21, 95% CI: 1.10-1.34) and individuals aged ≥55 years (OR = 1.18, 95% CI: 1.08-1.29), whereas no significant associations were found in female or younger populations. This study underscores the utility of the SIRI as a potential biomarker for CHD risk. The linear association between the SIRI and CHD risk emphasizes the importance of systemic inflammation, particularly in males and older adults. Further studies should investigate targeted anti-inflammatory interventions to potentially reduce CHD risk. However, due to the cross-sectional design of this study, it is important to note that no temporal or causal relationship can be inferred between SIRI levels and CHD risk intention-to-treat.

Neoplastic malignant tumors originating from inside the upper aerodigestive tract are referred to as lip, oral cavity, and pharyngeal malignancies. This study aimed to analyze the hospitalization profile for malignant neoplasms of the lip, oral cavity, and pharynx in Australia. This was a longitudinal ecological study that utilized the National Hospitals Data Collection in Australia database between 1998 and 2023. Hospitalization data were identified using the ICD codes C00-C14. Between 1998 and 2023, Australia reported a total of 160,055 hospitalization episodes. A large proportion of these admissions were overnight stays (69.7%). Most hospitalizations occurred among males (71.9%). The highest proportion of hospitalization episodes was amongst the 60 to 74 age group, who accounted for 39.8% of total episodes. Malignant neoplasm of other and unspecified parts of the tongue was the most common hospitalization reason, accounting for 14.5% of episodes. During the study period, the rate of same-day hospitalization increased by 55.9% (P < .001). However, the rates of overnight-stay-related hospitalization decreased by 9.7% (P < .001). Malignant neoplasms of the lip, oral cavity and pharynx are responsible for a sizeable healthcare burden among Australians, with the highest proportion of hospitalized cases occurring for males and those aged 60 to 74 years. There has been a significant increase in hospitalization involving same-day procedures. Investment in models of care offering same-day treatment and supportive care for older adults may contribute to mitigating inpatient pressures.

Background: The causal link between sleep duration and diverse health conditions remains unconfirmed. This meta-analysis aimed to clarify these relationships by synthesizing Mendelian randomization (MR) study evidence.

Methods: PubMed was systematically searched up to February 15, 2024, for MR studies exploring genetic predispositions to sleep duration/insomnia (short/long/overall sleep duration, insomnia) and associations with circulatory, digestive, neurodegenerative, metabolic diseases, and cancers. Eligible effect estimates were meta-analyzed.

Results: Fifty-one MR studies were included. Genetic variations in sleep traits were strongly linked to elevated risk of 12 cardiovascular diseases, obesity-related metrics (Type 2 diabetes, fasting glucose/insulin, HbA1c), neurological disorders (Alzheimer, amyotrophic lateral sclerosis, Parkinson disease), mental health conditions (attention-deficit/hyperactivity disorder, autism, bipolar disorder, major depressive disorder, schizophrenia), inflammatory bowel disease, and lung cancer.

Conclusion: Genetic evidence confirms causal associations between sleep characteristics and multiple diseases, emphasizing sleep's key role in health promotion and supporting personalized sleep management to reduce disease risk.

Background: The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has recently been discovered for gene editing and cancer therapy and its applications are expanding. This review and meta-analysis aim to assess the present and future of CRISPR/Cas9 based gene editing in cancer treatment and the way forward.

Methods: The search was conducted in PubMed from 2015 to 2025 and 89 relevant studies were identified. The study design, CRISPR/Cas9 targets, delivery methods, therapeutic efficacy and limitations were extracted from the studies.

Results: We reviewed the efficacy, challenges, and potential for translation of CRISPR/Cas9 in oncogene and tumor suppressor gene targeting and immune modulation. Several preclinical researches showed that CRISPR/Cas9 mediated disruption of oncogenes or restoration of tumor suppressor genes led to significant tumor regression. The evaluation was also extended to off target effects and integration with immunotherapy.

Conclusion: From the findings of this work, it can be concluded that CRISPR/Cas9 is a promising tool, but there are several limitations including off target effects, delivery systems and ethical issues that need to be solved in order to improve the clinical significance.

Objective: To analyze the current research status, hotspots and development trends in the field of immune response in the microenvironment after spinal-cord injury (SCI).

Methods: From January 1, 2005 to December 31, 2024, the literatures about immune response in microenvironment after SCI were retrieved from the core collection of Web of Science. The authors, countries, institutions, journals, co-cited literatures and keywords included in the literatures were visually analyzed by VOS viewer and bibliometrix, and the knowledge map was drawn.

Results: Analysis of 443 papers identified China and the US as leading contributors. Popovich PG emerged as a highly influential author, with the University of California System being the most productive institution. Key journals include Journal of Neuroinflammation and Brain Behavior and Immunity. Research hotspots center on macrophages, inflammation, and neutrophils, with microglia and central-nervous-system regulation playing significant roles in post-injury immune response.

Conclusion: Immune responses within the SCI microenvironment are a major research focus, shifting from mechanistic studies towards immunoregulatory strategies, aided by promising new technologies. Future progress requires enhanced multi-institutional collaboration and information sharing to accelerate research translation and improve patient recovery.