Annals of medicine最新文献

Background: West Nile virus (WNV) is among the most widespread arboviruses and has become a seasonal threat in temperate regions. Sustained in an enzootic bird-mosquito cycle, with humans and horses as incidental hosts, its geographic range has expanded in recent decades due to ongoing climatic and ecological changes. While most infections are asymptomatic or mild, a minority progress to neuroinvasive disease with high morbidity and long-term sequelae. This review summarizes current knowledge on epidemiology, pathogenesis, clinical spectrum, diagnostic challenges, therapeutic options, prevention, and research gaps.

Discussion: Lineages 1 and 2 co-circulate in Europe, where repeated large outbreaks highlight WNV adaptability to warmer summers, altered rainfall, and expanded mosquito habitats driven by recent ecological shifts. After inoculation, replication occurs in keratinocytes and dendritic cells, amplification in lymph nodes, and dissemination to visceral organs and the central nervous system. Neuroinvasion depends on viral proteins and host immune responses. Severe disease is associated with advanced age, immunosuppression, comorbidities, and genetic susceptibility. Clinical manifestations range from febrile illness to meningitis, encephalitis, or acute flaccid myelitis. Persistent neurological and functional sequelae are common, adding to disease burden. Diagnosis relies on molecular and serological tests, limited by short viremia and cross-reactivity with other flaviviruses. No approved antiviral therapy exists; management is supportive. Experimental antivirals, monoclonal antibodies, and interferon have shown mixed results. Vaccine candidates have progressed to phase 1-2 trials, but none are licensed for humans. Prevention relies on integrated vector control, veterinary surveillance, and donor screening, framed within a One Health approach.

Conclusion: WNV exemplifies the impact of global ecological change on zoonotic diseases. Strengthening surveillance, refining diagnostics, and advancing antivirals and vaccines through multidisciplinary collaboration are essential to mitigate future outbreaks.

Background: The lack of analysis methods and standardization are the core problems of serum free light chain (sFLC) detection in Multiple myeloma (MM). This study validated a new KHB sFLC assay through comparative analysis with conventional assays.

Materials and methods: Serum samples from 97 hospitalized MM patients were continuously collected. KHB, Freelite and N Latex assays were used to detect sFLC. The Bland-Altman and Passing-Bablok regressions were used for methodological comparison and bias evaluation. Spearman's test and Cohen's kappa coefficients were used to evaluate the correlation and clinical concordance.

Results: The sFLC results for KHB, Freelite, and N Latex showed a significant correlation. Passing-Bablok regression analysis revealed strong concordance between the KHB and N Latex for κFLC, and between KHB and Freelite assays for λFLC and FLC-ratio (κ/λ). When using N Latex and Freelite assays for sFLC determination, selecting iFLC/niFLC ≥ 20 or iFLC/niFLC ≥ 100 could lead to different clinical treatment decisions for approximately 9%∼12% of patients. When using KHB and Freelite assays for sFLC determination, selecting iFLC/niFLC ≥ 20 or iFLC/niFLC ≥ 100 could lead to different clinical treatment decisions for approximately 5%∼7% of patients.

Conclusion: KHB, as a sFLC detection method based on polyclonal antibodies and immunoturbidimetric principles, has a good correlation between its detection results and freelite and N Latex. The absolute difference in sFLC results among the three assays increased with increasing sFLC concentration, and selecting the same cutoff value for iFLC/niFLC may lead to inconsistent clinical treatment decisions in some patients.

Background: Hearing loss (HL) is the leading cause of disability worldwide, with a particularly severe impact on low- and middle-income countries and causing a huge economic burden. While child HL prevention exists, working-age adults (WAP) struggle to avoid occupational and environmental risks.

Method: Using Global Burden of Disease 2021 data, this study analyzed global HL prevalence trends in the WAP (1992-2021). Analyses included age-standardized prevalence rates (ASPR), estimated annual percentage change, and age-period-cohort (APC) modeling, stratified by gender, age, cause, severity, and Social Demographic Index (SDI).

Result: Global WAP HL prevalence significantly increased to 524 million in 2021 (a 56.9% increase since 1992), primarily due to population growth and aging. Age period cohort (APC) analysis revealed different patterns: as age increases, risk increases and cyclical effects generally increased (except in low SDI regions). The upward trend of birth cohorts in high to middle SDI countries was worrying. In addition, this study also observed that there was a gender difference in the prevalence trend of HL in WAP (male incidence rate was higher, but female growth was faster), and the patient population was gradually younger. Improved trends from 2017-2021 globally and regionally suggest a potential, albeit unexpected, positive influence of the COVID-19 pandemic on HL prevalence.

Conclusion: The global HL burden in the WAP is large and uneven, necessitating targeted interventions focusing on modifiable risks and SDI disparities. Further research is essential to understand the trends observed during the COVID-19 pandemic and to improve prevention strategies.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) and Neurally-Mediated Hypotension (NMH) are heterogeneous syndromes characterized by dysautonomia and multisystem symptoms. Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined.

Method: Patients from the Johns Hopkins POTS Clinic completed surveys assessing hives frequency and symptom burden using the Malmö POTS, the Composite Autonomic Symptom Score (COMPASS)-31, and a pain questionnaire. Associations between hives and clinical features were evaluated among patients with confirmed POTS, NMH, or clinically diagnosed orthostatic intolerance.

Result: Among 188 respondents, 80 (42.6%) reported hives sometimes and 33 (17.6%) reported hives often or always. Increasing hives frequency was associated with higher Malmö POTS scores and greater autonomic symptom burden across multiple COMPASS-31 subdomains, including gastrointestinal, bladder, and vasomotor symptoms (all p < 0.05). Hives was also associated with pain (OR 3.47, 95% CI 1.54-7.77, p = 0.002) and tingling (OR 5.73, CI 2.15-15.26, p < 0.001), but not orthostatic symptoms. These associations persisted after multivariable adjustment.

Conclusion: Hives are common in orthostatic intolerance syndromes and are associated with increased symptom burden. Future studies are needed to clarify the role of mast cell activation and evaluate mast cell-targeted therapies.

Background: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with a poor prognosis, and its molecular mechanisms remain unclear. Our previous research identified the signal sequence receptor subunit delta (SSR4) of the TRAP complex as a potential ESCC biomarker. The TRAP complex, composed of SSR1, SSR2, SSR3, and SSR4, is essential for protein translocation, folding, and quality control, crucial for cellular balance. While individual TRAP subunits have been studied, a comprehensive understanding of their roles in human diseases is lacking.

Aim: This review synthesizes current evidence on the TRAP complex and its subunits (SSR1-SSR4) to clarify their roles in tumor progression and other diseases, identify knowledge gaps, and evaluate their potential as therapeutic targets.

Results: The study shows that TRAP subunit genes are significantly upregulated in various cancers, influencing tumor progression and immune infiltration, with some subunits showing different responses to chemotherapy. A pan-cancer analysis highlights their roles, while SSR3 and SSR4 mutations are linked to congenital glycosylation disorders. SSR1 and SSR3 are essential for glucose metabolism and are associated with diabetes risk. The interaction between TRAP and endoplasmic reticulum stress suggests potential therapeutic applications.

Conclusion: This review emphasizes the crucial roles of the TRAP complex and its subunits (SSR1-SSR4) in various diseases, highlighting their potential as therapeutic targets and biomarkers. Future research should focus on understanding the mechanisms through integrated experimental and multi-omics approaches, defining subunit interactions, and exploring structure-based drug design for clinical applications.

Introduction: Whether intercostal nerve block can fully realize the prolonged analgesic potential of liposomal bupivacaine remains uncertain. This study aims to evaluate whether liposomal bupivacaine administered via intercostal nerve block confers a long-acting analgesic advantage over bupivacaine hydrochloride and no block within the postoperative 25-72 h window.

Patients and methods: This is a multicenter, randomized, parallel, three-arm controlled trial planning to enroll 210 patients undergoing elective unilateral video-assisted thoracoscopic surgery. Using center-stratified block randomization (1:1:1), patients will be allocated at the end of surgery to receive an intercostal nerve block with liposomal bupivacaine, bupivacaine hydrochloride, or no block. All patients will follow a standardized general anesthesia and multimodal analgesia protocol. The primary outcome is the area under the curve for pain scores during the postoperative 25-72 h. Other outcomes include pain verbal response scale at predefined time points, cumulative postoperative morphine milligram equivalent consumption, sensory block recovery time, 15-item quality of recovery scale, postoperative nausea and vomiting, postoperative pulmonary complications, length of hospital stay.

Discussion: This study prospectively evaluates the central question of whether liposomal bupivacaine confers a clinically meaningful long-acting analgesic advantage when used in the context of nerve block. By focusing on the area under the curve of pain scores and incorporating patient-centered outcomes such as opioid consumption and quality of recovery, the study aims to generate high-quality, translatable evidence to define the role of liposomal bupivacaine in thoracic surgery.

Clinical trial registration: Clinicaltrials.org, NCT07134660.

Objective: Hyperhomocysteinemia (Hcy) independently predicts coronary heart disease (CHD) and adverse cardiovascular events. Although folic acid plays a key role in Hcy metabolism, the effect of combined B-vitamin supplementation (folic acid, VB6, and VB12) on clinical outcomes in CHD remains uncertain.

Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted from inception through April 2025 using MeSH terms including "folic acid," "vitamin B6," "vitamin B12," "coronary heart disease," and "homocysteine." A random-effects model was used for meta-analysis.

Results: Thirteen studies involving 14,539 participants were included in the meta-analysis (7,338 patients treated with folic acid combined with vitamin B complex and 7,301 controls). Combined B-vitamin supplementation significantly reduced serum Hcy levels [mean difference: -2.36; 95% confidence interval (CI): (-3.09 to -1.62); p < 0.01] compared with any single-nutrient regimen. The incidence of vascular restenosis was lower in the intervention group than in the control group (risk ratio: 0.65; 95% CI: 0.44-0.95; p < 0.05). However, no significant differences were observed in the incidence of major cardiovascular events (p = 0.78) or cardiovascular-related mortality (risk ratio: 0.96; 95% CI: 0.85-1.07; p = 0.44).

Conclusion: Combined B-vitamin supplementation effectively lowers serum Hcy levels and the incidence of vascular restenosis in patients with CHD. However, its impact on cardiovascular events and mortality remains inconclusive.

Background: Head and neck squamous cell carcinoma (HNSCC) emerges from the mucosal linings of the paranasal sinuses, nasal cavities, oral cavity, nasopharynx, oropharynx, hypopharynx and larynx. Despite significant advances in understanding its epidemiology, pathogenesis and treatment strategies, the survival rate of HNSCC has shown little improvement over the last 40 years, maintaining a 5-year survival outcome of approximately 50%. Although the emergence of immunotherapies, such as pembrolizumab-FDA-approved for first-line HNSCC treatment-has shown promise in enhancing therapeutic outcomes and patient prognosis, merely a limited portion of individuals with HNSCC experience advantages from these therapeutic approaches.

Main body: Consequently, the need for novel biomarkers to refine treatment selection is increasingly urgent. The swift progress of artificial intelligence (AI) in medicine has enabled large-scale biomarker screening and the creation of predictive models, which are critical for identifying immunotherapy responders and predicting patient outcomes. This review summarizes current immunotherapeutic approaches in HNSCC and examines the role of AI in advancing immunotherapy strategies.

Discussion: Furthermore, it discusses the challenges, opportunities and strategies associated with integrating AI into clinical practice. Finally, the review highlights the transformative potential of AI in HNSCC immunotherapy and offers perspectives on its future applications.