BMC Medicine最新文献

Background: Gout is a crystal deposition disorder that leads to painful joint inflammation. Its mandatory precursor-hyperuricemia-may be associated with musculoskeletal pain even in the absence of gout attacks. The utilization of different analgesics in hyperuricemia patients has, however, not been previously studied. The objective of this study was to assess the use of analgesics in normouricemic and hyperuricemic individuals and to examine the modifying effect of renal function on analgesic use.

Methods: We utilized data from the GOAL (GOod Ageing in Lahti region) study, a prospective investigation of predominantly non-gouty individuals aged 52-76 years in Finland. Information on serum uric acid (SUA) levels, various other laboratory parameters, comorbidities, medication usage, lifestyle choices, and socioeconomic factors, was gathered. The glomerular filtration rate was estimated using the CKD-EPI creatinine-cystatin C equation (ml/min/1.73 m²). Individuals with SUA values exceeding 360 μmol/L (approximately 6 mg/dL) were identified as hyperuricemic, while those with an estimated glomerular filtration rate of 67 or lower (25th percentile) were classified as having diminished kidney function. Data on participants who had purchased prescription analgesics was gathered. Persons with neoplasms were excluded from the study. The results for analgesic purchases over an 11-year follow-up period were adjusted for age, sex, education, smoking status, alcohol consumption, body mass index, and physical activity.

Results: Purchases of non-steroidal anti-inflammatory drugs (NSAIDs) increased with rising SUA levels in individuals with normal kidney function (from ~ 400 to ~ 960 purchases per 1000 person-years between SUA 360 and 800 μmol/L), but no increase was observed in those with reduced kidney function. Purchases of other analgesics increased with higher SUA levels in both kidney function groups: from ~ 250 to ~ 800 purchases per 1000 person-years in individuals with normal kidney function and from ~ 400 to ~ 970 purchases per 1000 person-years in those with reduced kidney function. The inflection point was at SUA of 360 μmol/L in all groups where the association was observed.

Conclusions: Elevated SUA levels in our study associated with increase in the purchases of analgesics even among individuals without evidence of urate-lowering therapy use. For non-NSAID analgesics the association was detected in both persons with normal and reduced kidney function. This suggests that even in the absence of gout attacks, heightened SUA levels are associated with more frequent or intense pain, thereby increasing the demand for pain relief. Non-gouty hyperuricemia may not be asymptomatic.

Background: There is growing evidence that online food retail platforms (online food delivery, online grocery and meal kits) use a range of marketing techniques to promote unhealthy foods (energy-dense and nutrient-poor) to influence consumers' food choices and food purchases. However, existing literature on this topic is dispersed (across public health and marketing disciplines) and has not been synthesised from a public health perspective. The aim of this review was to synthesise the evidence on the digital marketing techniques prevalent on online food retail platforms, what food products they promote and their potential influence on consumers' online food purchase behaviours.

Methods: A mix of health and business databases was searched for peer-reviewed papers published in the last ten years, to align with the time from when online food retail platforms grew in popularity. Included studies were mapped to a pre-defined list of digital marketing techniques, marketing mix strategies and across Cialdini's principles of persuasion. All findings were described narratively.

Results: A total of 3408 studies were screened, of which 16 studies were included in the review. Eleven studies examined online food delivery services, and five studies examined online grocery retail services. A range of well-established digital marketing techniques were identified, including algorithmic personalisation, push notifications, membership-based models, interactive tools such as sorting and filtering features, hyperlinks or prompts to create combo deals, site customisation offering personalised shopping experience, clickable banner advertisements and search engine optimisation. Whilst these are standard techniques in digital commerce, we found that they were often deployed to preferentially promote nutrient-poor foods. Specifically, seven studies highlighted the use of these marketing techniques to promote foods of poor nutritional quality, with marketing strategies reinforcing perceptions of value, tastiness and pleasure. Only two studies examined and reported a positive influence of using price promotion techniques on consumers' unhealthy food purchase intention.

Conclusions: Online food delivery and online grocery platforms use a range of digital marketing techniques to deliver content in highly persuasive ways, often promoting unhealthy food options. Future research should explore how these platforms can be leveraged to enable healthier population food choices and align with public health objectives.

Background: Social isolation and loneliness have emerged as important modifiable risk factors for mental disorders, posing significant public health challenges. However, they have not been comprehensively investigated in relation to multisystemic diseases and their temporal trajectories. We aimed to systematically identify the health outcomes associated with social isolation and loneliness and characterize their disease trajectories and comorbidity networks.

Methods: A total of 466,547 participants (mean age: 56.5 ± 8.1, 54.6% females) with available information on social isolation and loneliness were included from the UK Biobank between 2006 and 2010 and followed up until 2022. Social isolation was measured using a composite score derived from three questions on number in household, frequency of friend and family visits, as well as participating in leisure and social activities. Loneliness was assessed by the subjective perception of feeling lonely and the willingness to confide in others. A total of 246 medical conditions were included in phenome-wide association analyses. Disease trajectory and comorbidity network analyses were performed to identify sequential patterns and visualize disease clusters.

Results: During an average medium follow-up of 11.7 years, social isolation was found to be significantly associated with increased risks of 28 medical conditions, and loneliness with 80. The strongest association for both exposures was with personality disorders, with respective hazard ratios of 2.12 (95% CI, 1.59-2.82) for social isolation and 2.62 (95% CI, 1.90-3.61) for loneliness. The conditions covered a broad spectrum, including respiratory, neurological, digestive, musculoskeletal, and genitourinary diseases and mental disorders. Three main disease clusters were identified in relation to social isolation and eight disease clusters were related to loneliness. Septicemia and alcohol-related disorders as the initial condition was notably observed in the disease cluster trajectories of both social isolation and loneliness. Subsequently, the comorbidity network revealed three and five distinct comorbidity modules associated with social isolation and loneliness, respectively. The disease nodes within these modules exhibited structural consistency with those within the disease trajectory clusters.

Conclusions: These findings highlight the importance of integrating screening, interventions, and referrals for social isolation and loneliness into health care system to prevent the adverse health conditions.

Background: Redundant publication, the practice of submitting the same or substantially overlapping manuscripts multiple times, distorts the scientific record and wastes resources. Since 2022, publications using large open-science data resources have increased substantially, raising concerns that Generative AI (GenAI) may be facilitating the production of formulaic, redundant manuscripts. In this work, we aim to quantify the extent of redundant publication from a single, large health dataset and to investigate whether GenAI can create submissions that evade standard integrity checks.

Methods: We conducted a systematic search for the years 2021 to 2025 (year to end-July) to identify redundant publications using the US Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) dataset. Redundancy was defined as publications analysing the same exposures associated with the same outcomes in the same national population. To test whether GenAI could facilitate creating these papers, we prompted large language models to write three synthetic manuscripts using redundant publications from our dataset as input, instructing them to maximise syntactic differences and evade plagiarism detectors. These three synthetic manuscripts were then tested using a leading plagiarism detection platform to assess their similarity scores.

Results: Our search identified 411 redundant publications across 156 unique exposure-outcome pairings; for example, the association between oxidative balance score and chronic kidney disease using NHANES data was published six times in 1 year. In many instances, redundant articles appeared within the same journals. The three synthetic manuscripts created by GenAI to evade detection yielded overall similarity scores of 26%, 19%, and 14%, with individual similarity contributions below the typical 5% warning thresholds used by plagiarism detectors.

Conclusions: The rapid growth in redundant publications (a 17-fold increase between 2022 and 2024) suggests a systemic failure of editorial checks. These papers distort meta-analyses and scientometric studies, waste scarce peer review resources, and pose a significant threat to the integrity of the scientific record. Current checks for redundant publications and plagiarism are no longer fit for purpose in the GenAI era; greater co-operation between publishers and modified guidelines will be needed to address new innovations in paper mill production.

Background: Although the 2021 European Society of Cardiology (ESC) guidelines and Systematic COronary Risk Estimation 2 (SCORE2) models provide structured risk assessment, their complexity may hinder routine use. The web-based platform HUMTELEMED was developed to integrate cardiovascular risk (CVR) stratification and therapeutic targets in a user-friendly interface. We evaluated CVR distribution, the proportion of patients meeting LDL-cholesterol (LDL-C) and blood pressure (BP) goals, and the use of lipid- and BP-lowering therapies in a large Italian cohort.

Methods: This cross-sectional study included 7260 anonymised adults aged ≥ 40 years who accessed the platform between December 2022 and September 2024. Most were in primary prevention, without established CV disease (99.5%, n = 7224). CVR was stratified using SCORE2, SCORE2-Older People (OP), and 2021 ESC charts. Proportions of patients meeting guideline-based LDL-C and BP goals were also assessed overall and in subgroups.

Results: Mean age was 59.4 ± 11.8 years; 55.3% (n = 4046) were male, 46.5% (n = 3373) had hypertension, 18.3% (n = 1298) obesity, 8.5% (n = 617) diabetes, 11.8% (n = 860) chronic kidney disease, 16.0% (n = 1165) peripheral artery disease, and 37.2% (n = 2705) reported smoking. CVR distribution was 21.9% (n = 1593) low-to-moderate, 38.1% (n = 2764) high, and 40.0% (n = 2903) very high/extreme. LDL-C goals were met by only 11.3% (n = 819) overall and 15.9% (n = 342) of those on LLT. BP goals were met by 75.6% (n = 5492) overall, and by 68.3% (n = 2304) of patients on antihypertensive therapy. Goal meeting declined with increasing CVR: LDL-C, 44.8% low-to-moderate vs. 13.8% high vs. 11.6% very high/extreme (p < 0.001); BP, 89.5% vs. 78.6% vs. 65.4% (p < 0.001). Subgroup analyses showed lower proportions meeting LDL-C and BP goals in men (10.6% vs. 12.0% and 73.1% vs. 78.7%, respectively; p < 0.001), older adults (10.6% vs. 11.4% and 70.8% vs. 76.9%, respectively; p < 0.001), and individuals with obesity (9.0% vs. 13.8% and 63.0% vs. 83.1%, respectively; p < 0.001).

Conclusions: In this large real-world Italian cohort, the proportion of patients meeting LDL-C and BP goals was critically low, particularly among those at the highest CVR, despite pharmacological treatment. These findings highlight the urgent need for improved implementation of guideline-based prevention strategies, including greater use of combination therapies, better risk communication, and stronger adherence to ESC recommendations.

Background: KL130008 is a selective Janus kinase 1/2 inhibitor with encouraging preclinical efficacy. Phase I trials in healthy volunteers and patients with rheumatoid arthritis (RA) showed favorable pharmacokinetics, dose-dependent inhibition of phosphorylated signal transducer and activator of transcription 3, good tolerability, and no clinically meaningful pharmacokinetic interaction with methotrexate, supporting further evaluation in active RA.

Methods: In this double-blind, placebo-controlled phase II trial at 24 centers in China, RA patients were randomized (1:1:1:1) to receive placebo or KL130008 capsules (0.5, 1 or 2 mg) once daily for 12 weeks. Week 13-24, the placebo group was switched 1:1 to KL130008 at 0.5 mg or 1 mg, while other groups continued their original doses. All patients received 7.5-25 mg methotrexate once weekly throughout 24 weeks. The primary outcome was the proportion of patients who achieved at least 20% improvement in American College of Rheumatology criteria (ACR20) after 12 weeks of treatment. Secondary outcomes included ACR50/70 responses, Disease Activity Score 28 (DAS28) changes, safety assessments and pharmacokinetic properties.

Results: By week 12, the proportion of patients achieving ACR20 was significantly lower in the placebo group (26.8%) than in the groups receiving KL130008 at 1 mg (55.0%, p = 0.011) or 2 mg (64.1%, p = 0.001). KL130008 at 2 mg also significantly outperformed placebo for ACR50 or ACR70 responses, DAS28-C-reactive protein, DAS28- erythrocyte sedimentation rate, and the Health Assessment Questionnaire Disability Index scores. The clinical benefits of KL130008 persisted through week 24 and were associated with markedly lower levels of tumor necrosis factor-a and interleukin-6 in blood, without affecting levels of interleukin-15. The oral drug showed linear pharmacokinetics and mild accumulation. During the 24-week treatment, drug-related treatment-emergent adverse events occurred in approximately half of the patients receiving KL130008 (52.5%, 50.0%, and 56.4% in the 0.5, 1, and 2 mg groups), and the most frequent events were anemia and hyperlipidemia.

Conclusions: KL130008 demonstrated potential for sustained efficacy and safety in the treatment of RA.

Trial registration: Registered in the Chinese Clinical Trial Register (ChiCTR2100042141).

Background: White adipose tissue (WAT) dysfunction including an aberrant expression of miRNAs is strongly associated with the risk of developing type 2 diabetes (T2D), with limited evidence linking early changes in the WAT-derived miRNAs and T2D. The present study aims to identify early miRNome changes prognostic for T2D in mice and humans.

Methods: Gonadal (g) WAT of diabetes-resistant and diabetes-prone mice were subjected to multi-omics analyses (transcriptome, miRNome, methylome, proteome). Metabolic phenotypes linked with T2D were correlated with adipose tissue miRNA expression and DNA methylation from 14 monozygotic twin pairs discordant for T2D. Plasma miRNA levels from females at high risk of developing T2D (TÜF study) were included.

Results: Adipose tissue of the diabetes-susceptible mice was less insulin sensitive with ~ 200 differentially expressed mature miRNAs compared to diabetes-resistant mice. Integrative analysis of miRNome-transcriptome-proteome identified 227 proteins involved in amino acid metabolism, inflammation, signalling pathways, and insulin resistance. More than 20 differentially expressed miRNAs are located in the imprinted region Dlk1-Gtl2 and Mest (miR-335) potentially regulated by DNA methylation. Imprinted miRNAs also exhibited similar alterations in adipose tissue from monozygotic twin pairs discordant for T2D, with miR-335 expression altered only in females. Moreover, plasma levels of miR-335-5p were negatively correlated with fasting blood glucose in females at high risk of developing T2D.

Conclusions: Early alterations of WAT-derived miRNAs such as miR-335-5p could contribute to systemic metabolic changes associated with the risk of developing T2D.

Background: Neonatal jaundice (NJ), characterized by significantly increased bilirubin levels, is a prevalent global neonatal condition affecting 60-80% of newborns. It imposes long-term adverse effects on neurodevelopment and overall health. Current clinical treatments, such as phototherapy, primarily focus on symptom management, whereas the preventive strategies for NJ remain largely lacking. Infant breastfeeding is associated with NJ. However, whether maternal probiotics use and infant colostrum feeding may reduce the NJ risk has yet to be determined and warrants further investigation in large-scale cohorts. Therefore, this study aimed to evaluate whether they have any preventive effect.

Methods: We investigated the relationship of maternal probiotic intake and baby feeding type with NJ onset using the CHILD cohort, a prospective birth cohort recruited 3624 mothers and 3542 paired infants. Probiotic intake during pregnancy and its patterns (increased, maintained, or decreased compared to preconception) were obtained via questionnaires. The NJ conditions (yes/no) and feeding modes (exclusive colostrum, formula-only, or mixed feeding) were collected from hospital birth records. Bivariate and multivariable logistic regressions were employed to evaluate the risk using adjusted odds ratio (AOR) with 95% confidence intervals (CI) after adjustment for confounders. P < 0.05 indicates statistical significance.

Results: A total of 2596 healthy controls and 433 NJ cases with complete data were included from the CHILD cohort for analysis. Interestingly, probiotic intake during pregnancy was associated with a remarkably reduced odds of NJ (AOR 0.78 (0.61, 0.98), P = 0.041) compared to participants who never used probiotics. Neonates with exclusive colostrum feeding also had a significantly lower incidence of NJ than other feeding modes (AOR 0.34 with (95%CI) (0.27,0.44), P < 0.001). Further stratification analysis on probiotic intake showed that mothers who increased (AOR 0.53 (0.32, 0.89), P = 0.016) or maintained (AOR 0.44 (0.24, 0.80), P < 0.007) probiotic intake during pregnancy had a lower risk of NJ compared to those who decreased intake.

Conclusions: This cohort-based evidence highlights that maternal probiotic intake and exclusive colostrum feeding are important modifiable factors associated with reduced NJ risk.

Background: Intracerebral hemorrhage (ICH) is a challenging and life-threatening stroke subtype. Normobaric hyperoxia (NBO) is a promising therapeutic strategy for ICH. Herein, we evaluated the safety and efficacy of NBO in patients with ICH.

Methods: In this randomized, controlled, two-arm (1:1 ratio), open-label clinical trial, participants were randomly assigned to either the NBO group (100% O₂ at 8 L/min for 1 h per session, four times daily, for 7 days) or the control group (100% O₂ at 2 L/min continuously for 24 h daily for 7 days). The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-3 at 90 days. The results are presented as the risk ratio (RR) with 95% confidence intervals (95% CI). P < .05 indicated statistical significance.

Results: A total of 96 patients were enrolled (NBO, n = 48; control, n = 48). The proportion of patients who achieved an mRS score of 0-3 at 90 days was significantly higher in the NBO group than in the control group (81.3% vs. 56.3%; unadjusted RR, 1.44; 95% CI, 1.09-1.92; unadjusted P = .01; adjusted RR, 1.39; 95% CI, 1.06 to 1.82; adjusted P = .02). Additionally, the 90-day Barthel Index scores on days 7 and 14 were significantly higher in the NBO group (all P < .05). Imaging assessments revealed that both absolute and relative perihematomal edema at 7 and 14 days were reduced in the NBO group, and perfusion in the region surrounding the hematoma was improved at 7 days compared to that in the control group (all P < .05). No significant differences in oxygen-related complications were observed between the two groups (all P > .05).

Conclusions: Early intermittent administration of NBO in patients with ICH may improve 90-day outcomes without increasing the risk of death or other oxygen-related complications.

Trial registration: NCT04144868.

Background: Heart failure (HF) represents the end stage of cardiovascular diseases with high mortality and limited treatment options. Cyclophilin B (CypB), known mainly as an endoplasmic reticulum chaperone, has been implicated in cardiovascular diseases. But the role of CypB in HF remains unclear.

Methods: Transverse aortic constriction (TAC) surgery on mice in vivo was conducted to model cardiac hypertrophy (CH) and HF, and angiotensin II (Ang II) was applied to neonatal rat cardiomyocytes in vitro to mimic cardiomyocyte hypertrophy. The effects of CypB deficiency on CH/HF were evaluated by echocardiography, tissue staining, and molecular expression assays. The mechanism of CypB action was elucidated by RNA sequencing, bioinformatics analysis, mitochondrial function assay, immunofluorescence staining, glucose uptake assay, PET/CT scan, transcription factor analysis, dual luciferase reporter assay, Cut&Run-qPCR assay, STAT3 inhibitor, and overexpression virus.

Results: Increased expression of CypB has been observed in hypertrophied and failing hearts. CypB deficiency improves cardiac function, reduces hypertrophy after TAC surgery, and attenuates Ang II-induced cardiomyocyte hypertrophy. Mechanistically, CypB deletion increases AMPK phosphorylation, enhances the expression of glucose transporter type 1 (GLUT1), glucose transporter type 4 (GLUT4), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and downstream signaling molecules, thereby promoting cardiac glucose catabolism and mitochondrial function. STAT3 transcriptionally activates CypB expression, STAT3 inhibition ameliorates TAC-induced heart failure, and CypB deficiency reverses STAT3 overexpression-induced HF.

Conclusions: CypB deficiency ameliorates CH and HF by enhancing cardiac energy production, providing a potential therapeutic target for CH and HF.