搜索结果：Frontiers in medicine

This study aimed to comprehensively investigate the shared molecular mechanisms and intercellular communication signatures of gout and metabolic syndrome (MetS), seeking to identify and validate key regulatory genes and pathways for developing precise diagnostic and therapeutic strategies. Transcriptomic datasets for gout and MetS were retrieved from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (CODEGs) were identified through integrative analysis, followed by the construction of protein-protein interaction (PPI), drug-gene, and competing endogenous RNA (ceRNA) networks to pinpoint hub genes and regulatory axes. Single-cell RNA sequencing data were analyzed to map hub gene expression and cell-cell communication patterns. Crucially, key bioinformatic predictions were validated in established in vitro cell models of gout and MetS using quantitative real-time PCR (qPCR) and Western blot analysis. A total of 261 CODEGs were identified, leading to the selection of 19 hub genes, including JAK1 and CSF1R. Functional enrichment analysis revealed their primary involvement in immune activation and inflammatory signaling, such as the JAK-STAT pathway. Experimental validation confirmed these findings: qPCR analysis demonstrated that the mRNA levels of JAK1, CSF1R, and NAMPT were significantly elevated in cellular models simulating both gout and MetS conditions. Furthermore, Western blot analysis revealed increased protein expression of JAK1 and CSF1R, alongside a marked increase in phosphorylated STAT3 (p-STAT3), indicating activation of the JAK-STAT pathway at the signaling level in both conditions. Single-cell analysis showed that JAK1 and CSF1R were predominantly expressed in natural killer (NK) cells and monocytes, respectively. Cell communication analysis highlighted monocytes and neutrophils as central hubs in gout, while smooth muscle cells and hematopoietic stem cells were dominant in MetS. Notably, the VISFATIN signaling pathway was highly active in both diseases, with NAMPT-associated ligand-receptor interactions, including NAMPT-(ITGA5 + ITGB1) in gout and NAMPT-INSR in MetS. This study, through integrated multi-omics analysis and experimental validation, identifies and characterizes a shared molecular landscape between gout and MetS. We highlight the potential roles of JAK1 and CSF1R in a shared inflammatory context, associated with activation of the JAK-STAT pathway at the signaling level. Our findings suggest that the VISFATIN signaling axis may represent a common link and delineate NAMPT-associated communication networks. These results provide insights into the intertwined pathophysiology of gout and MetS, and may offer promising avenues for joint therapeutic interventions.

Diabetic foot ulcers represent a significant clinical challenge requiring comprehensive knowledge of classification systems and surgical intervention strategies. The BOPPPS (Bridge-in, Objective, Pre-assessment, Participatory learning, Post-assessment, Summary) teaching model has gained increasing attention in medical education, yet its effectiveness in vascular surgery residency training remains underexplored. This study aimed to evaluate the effectiveness of the BOPPPS teaching model in standardized training for vascular surgery residents regarding diabetic foot Wagner classification and surgical intervention strategies. This retrospective cohort study included 196 vascular surgery residents who underwent standardized training at the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University from January 2023 to December 2024. Based on their training rotation schedule, residents were allocated to either an experimental group (n =&#x202f;98) receiving BOPPPS-based instruction or a control group (n =&#x202f;98) receiving traditional teaching methods. Primary outcomes included theoretical examination scores, clinical skill assessment (Mini-CEX and DOPS), self-directed learning readiness (SDLRS), critical thinking disposition (CTDI-CV), and teaching satisfaction. The experimental group demonstrated significantly higher theoretical examination scores (82.47&#x202f;&#xb1;&#x202f;8.63 vs. 74.85&#x202f;&#xb1;&#x202f;9.21, p&#x202f;<&#x202f;0.001) and Mini-CEX scores (7.84&#x202f;&#xb1;&#x202f;1.12 vs. 6.93&#x202f;&#xb1;&#x202f;1.28, p&#x202f;<&#x202f;0.001) compared to the control group. DOPS scores for wound debridement (8.12&#x202f;&#xb1;&#x202f;0.95 vs. 7.23&#x202f;&#xb1;&#x202f;1.18, p&#x202f;<&#x202f;0.001), vascular assessment (7.96&#x202f;&#xb1;&#x202f;1.08 vs. 7.14&#x202f;&#xb1;&#x202f;1.25, p&#x202f;<&#x202f;0.001), and amputation level determination (7.78&#x202f;&#xb1;&#x202f;1.15 vs. 6.89&#x202f;&#xb1;&#x202f;1.32, p&#x202f;<&#x202f;0.001) were significantly improved in the BOPPPS group. Self-directed learning readiness scores increased significantly in the experimental group (168.52&#x202f;&#xb1;&#x202f;18.74 vs. 153.28&#x202f;&#xb1;&#x202f;21.36, p&#x202f;<&#x202f;0.001), and critical thinking disposition scores were notably higher (292.84&#x202f;&#xb1;&#x202f;28.65 vs. 271.35&#x202f;&#xb1;&#x202f;31.42, p&#x202f;<&#x202f;0.001). Teaching satisfaction rates reached 94.9% in the experimental group versus 78.6% in the control group (p&#x202f;<&#x202f;0.001). The BOPPPS teaching model significantly enhances the effectiveness of standardized training for vascular surgery residents in diabetic foot management, improving theoretical knowledge, clinical competence, self-directed learning ability, and critical thinking disposition.

SARS-CoV-2 has been responsible for a worldwide public health crisis and a pandemic that began in February 2020, with approximately 679 million cases and over 6.7 million deaths to date. Despite the existence of approved COVID-19 vaccines, these vaccines are either based on mRNA technology or viral vectors. Imam Abdulrahman Bin Faisal University (IAU) has developed a thermally stable plasmid DNA (pDNA)-based vaccine candidate using a platform approach that enables the rapid development of vaccines against emerging viral diseases. The pDNA vaccine developed by IAU encodes the full-length, optimized version of the SARS-CoV-2 Spike protein. Key advantages of this pDNA vaccine are that it is cost-effective, thermally stable, and can be used to administer multiple immunizations without incurring anti-vector responses, making it a promising candidate as a vaccine booster dose. This study aims to investigate the safety, tolerability, and immunogenicity of this prophylactic pDNA vaccine as a booster vaccine to protect against COVID-19 when administered as an intramuscular injection in a single ascending dose design. In total, 42 eligible healthy subjects will be enrolled in the study. The subjects will be randomized to receive either the investigational vaccine or placebo (Saline) at a 3:1 allocation ratio. Participants will have received two doses of a SARS-CoV-2 mRNA vaccine at least 4 months prior to enrollment. Subjects will be enrolled in a dose-escalating study and assigned to one of the three cohorts (Cohort 1: low-dose; Cohort 2: mid-dose; Cohort 3: high-dose). Primary endpoints will include local reactions and systemic reactions for up to 7 days following vaccination, adverse events from vaccination to 1 month, and serious adverse events from vaccination to 6 months. Secondary endpoints will include the evaluation of binding antibody (bAB) and neutralizing antibody (nAB) responses at vaccination day (Visits 1) and 30 days after vaccination (Visit 4), the ratio of bAB to nAB titers at Visits 1 and 4, and cellular immune responses (CD3, CD4, CD8, CD45RA, CCR7, IFN-&#x3b3;, IL-2, IL-4, IL-13, and TNF) at Visits 1 and 4. The study will be critical to determine the safety and immunogenicity of the pDNA vaccine in participants who have previously received a COVID-19 mRNA vaccine. This study will also aim to determine the safest maximum tolerated dose in participants receiving the pDNA vaccine. ClinicalTrials.gov SCTR No 23010802.

Post-mastectomy pain syndrome (PMPS) is a common and disabling complication after breast cancer surgery. Although traditionally categorized as neuropathic or nociceptive, many patients present with overlapping features consistent with mixed pain, a phenotype that remains poorly defined in clinical practice. We performed a retrospective analysis of prospectively maintained data from women with refractory PMPS referred to a tertiary cancer-related pain clinic between January 2022 and September 2025. Pain was classified as nociceptive, neuropathic, or mixed based on structured clinical assessment. Patient-reported measures included the Brief Pain Inventory (BPI) and Pain Catastrophizing Scale (PCS). Multivariable logistic regression was used to examine factors independently associated with mixed pain. One hundred twenty women (mean age 57.9 &#xb1; 12.5&#x202f;years) were included. Pain phenotypes were nociceptive in 40.8%, neuropathic in 25.0%, and mixed in 34.2%. Pain intensity, interference, and catastrophizing scores were elevated across groups without statistically significant differences (all p > 0.05). In adjusted analyses (analytic N = 113), multiplicity of pain sources (&#x2265;2 concurrent pain generators; adjusted OR 49.96; 95% CI 11.69-213.41) and radiotherapy-attributed pain (adjusted OR 5.75; 95% CI 1.15-28.82) were independently associated with mixed pain. Model stability was evaluated in sensitivity analyses using Firth's penalized likelihood logistic regression. In this tertiary cohort of women with refractory PMPS, mixed pain accounted for approximately one-third of cases and was independently associated with multiple concurrent pain sources and radiotherapy-attributed pain. These findings suggest that the coexistence of multiple pain sources, rather than pain severity alone, may characterize mixed pain presentations. Given the observational design and model limitations, results should be interpreted as hypothesis-generating. Mechanism-based assessment may help inform individualized management strategies.

Tick-associated illnesses are increasingly recognised in Australia, yet the epidemiology and clinical manifestations of Borrelia burgdorferi sensu lato remain uncertain in the absence of confirmed local isolates and reliance on diagnostics validated for European and North American strains. These limitations complicate interpretation and may contribute to delayed recognition of systemic manifestations, with potential progression to Debilitating Symptom Complexes Attributed to Ticks (DSCATT). We describe a case consistent with European-profile Borrelia infection presenting with early inflammatory myocarditis evolving to mild cardiomyopathy and complete clinical and immunologic recovery after antimicrobial therapy. The patient had recent travel to tick-endemic regions of Scandinavia (Denmark and Sweden) in mid-July 2022 and subsequently developed symptoms following reported tick exposure at North Head, Sydney. Symptom onset occurred on 16 August 2022. The first serology, which was reactive, was obtained 13&#x202f;weeks after symptom onset and demonstrated broad IgG reactivity (VlsE variants, OspC, p58, p39), fulfilling CDC two-tier and EUCALB immunoblot criteria for disseminated Borrelia infection. Whole-blood multiplex PCR was negative. Treatment comprised 28&#x202f;days of intravenous ceftriaxone followed by 12&#x202f;weeks of doxycycline. Immune-mediator profiling identified an early pro-inflammatory signature (IL-6, TNF-&#x3b1;, IFN-&#x3b3;) with concurrent lymphoid activation (TNF-&#x3b2;) and prominent endothelial activation (fractalkine), followed by a dominant reparative vascular profile characterised by PDGF-AA, EGF, and sCD40L. Clinical indices improved substantially, with Horowitz Questionnaire Score decreasing from 47 to 18 and Karnofsky Performance Status increasing from 70 to 100 by Month 12. Serologic contraction and immune normalisation paralleled clinical recovery. Immune-cell kinetics aligned with cytokine-defined cluster transitions (B1/B3 inflammatory activation to B2/H vascular-repair programming), with early redistribution and reduced circulating B cells and NK cells followed by recovery to low-normal ranges by 12-24&#x202f;months. At the systemic level, leukocyte counts showed early leukocytosis, mid-course suppression during stromal-vascular repair, and complete normalisation, consistent with immune containment without persistent inflammation. The mature serologic and immunologic profile does not distinguish between infection acquired during European travel or subsequent Sydney exposure, and local transmission cannot be inferred. This case illustrates probable Borrelia-associated inflammatory cardiomyopathy with full resolution and highlights the value of integrated serologic and immune-signature profiling in complex tick-associated presentations.

To evaluate the effects of pelvic drainage and postoperative rectal misoprostol on short-term outcomes after laparoscopic myomectomy. Multicenter retrospective observational cohort study. Five tertiary hospitals in Sichuan Province, China, between January 2021 and June 2025. Of 302 patients initially identified, 280 met inclusion criteria after exclusions for malignancy, incomplete data, or combined procedures. Patients were categorized into four groups according to surgical approach (multi-port vs. single-port) and postoperative management strategy, allowing evaluation of the independent effects of pelvic drainage and misoprostol within different surgical contexts. The use of pelvic drainage and rectal misoprostol (400&#x202f;&#x3bc;g) was non-randomized and determined by institutional protocol and surgeon discretion. Perioperative parameters-including operative time, blood loss, drainage characteristics, and postoperative recovery-were extracted from electronic medical records. The primary outcomes were postoperative fever and pelvic infection; secondary outcomes included drainage output and duration, postoperative pain, and length of hospital stay. Pelvic drainage did not reduce postoperative fever or pelvic infection. In multivariable logistic regression adjusted for relevant covariates (including age, BMI, parity, prior abdominal surgery, myoma size, number of myomas removed, and use of vasopressin or other hemostatic agents), drain placement independently increased the risk of postoperative fever (adjusted OR&#x202f;=&#x202f;2.30, 95% CI 1.10-4.82, p&#x202f;=&#x202f;0.028). In contrast, postoperative rectal administration of misoprostol significantly decreased the risk of postoperative fever (adjusted OR&#x202f;=&#x202f;0.53, 95% CI 0.30-0.96, p&#x202f;=&#x202f;0.031) and pelvic infection (adjusted OR&#x202f;=&#x202f;0.36, 95% CI 0.12-0.97, p&#x202f;=&#x202f;0.043). Among patients with drainage, misoprostol use further reduced total drain volume and duration (both p&#x202f;<&#x202f;0.05). Patients undergoing single-port procedures without drainage also showed low complication rates, with less postoperative pain and shorter hospital stays compared with multi-port cases with drains (all p&#x202f;<&#x202f;0.05). Pelvic drainage after laparoscopic myomectomy offers no measurable benefit and may heighten postoperative morbidity. In contrast, adjunctive rectal misoprostol effectively lowers the incidence of postoperative fever and pelvic infection.

Cesarean section (CS) rates have risen globally to unprecedented levels, becoming a major public health concern. T&#xfc;rkiye has one of the highest CS rates among OECD countries, reaching approximately 57%, far above World Health Organization recommendations. In response, the Ministry of Health introduced the Normal Birth Action Plan (NBAP) in October 2024 to promote vaginal birth (VB) and reduce medically unnecessary CS. However, the real-world impact of NBAP in private hospitals-where maternal preference, fear of childbirth, institutional dynamics, and medico-legal concerns strongly influence mode of birth-remains unclear. To evaluate the early effects of NBAP on mode of birth distribution in a private hospital and to examine CS indications, maternal preference, and the role of NBAP-related counseling. This retrospective single-centre study included 2,226 births between October 2023 and October 2025, comparing 1-year pre-NBAP and post-NBAP periods. Maternal age, mode of birth, CS type, CS indication, and NBAP counseling status were analyzed. Categorical variables were compared using chi-square tests, with p < 0.05 considered statistically significant. Mean maternal age was 27.37 &#xb1; 5.04 years (range: 18-43). CS rates decreased from 89% in the pre-NBAP period (1215/1365) to 81% in the post-NBAP period (698/861), representing a reduction in CS rate from 89% to 81%, alongside a decrease in absolute CS numbers, which should be interpreted in the context of reduced total births. VB increased from 11% to 19% (an 8%-point increase). CS attributed to maternal request or fear of VB declined from 26.1% to 17%. Mode of birth and CS indications differed significantly between periods (p < 0.001). Similar trends were observed across age groups (18-30 vs. &#x2265;31 years). Monthly analyses showed a gradual increase in VB following NBAP implementation. Total births decreased by approximately 37% during the post-NBAP period, suggesting additional contextual or demographic influences. In this private hospital cohort, the post-NBAP period was temporally associated with a reduction in cesarean births and an increase in vaginal births, along with a decrease in CS attributed to maternal request or fear of VB. However, given the retrospective design and concurrent changes in birth volume, causality cannot be inferred. Multicentre studies with longer follow-up are required to clarify these associations.

Gastrointestinal cancer (GC) is particularly malignant as they tend to progress slowly before advanced stages due to the forecast of early-specific symptoms. The heterogeneous properties of GCs require extremely precise and sensitive diagnostic techniques that can integrate in-depth structural information and surface-level data to distinguish cancer severity grades, thereby significantly lowering mortality rates. Deep learning (DL) algorithms are crucial in the classification of these various GC grades. However, the algorithms cannot detect interpretability and are characterized by a high probability of false alarm rates in detecting the underlying acute relationship between the medical images. Additionally, existing systems lack language-level transparency, preventing them from generating user-based narrative diagnostic explanations consistent with medical standards. To address this aforementioned challenge, this research study introduces a novel explainable LLM (X-LLM) based DL framework, which overcomes the drawbacks of existing DL algorithms. The suggested framework uses the ensemble transformer architectures that combine the clinical features by integrating the endoscopy and computer tomography (CT) scan images for enhancing the performance in detecting the different severity grades of GCs. The proposed system uses several components: (1) heterogeneous image collection; (2) image pre-processing; (3) ensemble networks; (4) interpretability analysis; and (5) user-interaction module. The extensive experiments are conducted utilizing two different datasets, such as Kvasir and TCIA CT (TCGA-STAD) scan images. The severity annotation of both datasets was carried out by experienced medical doctors, including endoscopists. Several evaluation metrics, including accuracy, precision, and recall, are measured and benchmarked against other learning networks. The experimental findings demonstrate the enhanced performance of the proposed framework over the existing models by achieving the accuracy, precision, recall, and F1-score values of 0.99, 0.997, 0.99, and 0.99, respectively. Furthermore, different LLM models such as GPT4.0, GPT3.5, LLAMA, and GEMINI are integrated, and their mode of interaction is also analyzed with SHAP measurements. The suggested framework demonstrates its strong potential by enhancing diagnostic performance, achieving high performance with user-interacted clinical treatment outcomes.

Pemetrexed is a folate-pathway-targeting antineoplastic agent widely used in non-squamous non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma. We used the US Food and Drug Administration Adverse Event Reporting System (FAERS) to characterize pemetrexed-associated adverse events to inform clinical safety monitoring. Pemetrexed-related reports were retrieved from the FAERS database from first quarter of 2004 through the fourth quarter of 2024. All reports were coded using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. We performed descriptive analyses and disproportionality analyses using reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM), and Bayesian confidence propagation neural network (BCPNN; information component [IC]) to identify safety signals. Statistical significance was defined as ROR >1 with the lower 95% confidence interval (CI) >1. We identified 27,098 pemetrexed-associated reports in the FAERS database (2004-2024), in which pemetrexed was designated as the primary suspect drug. Signal detection based on these reports identified 653 significant signals of disproportionate reporting (SDR) spanning 27 System Organ Classes (SOCs). The strongest signals occurred in Blood and Lymphatic Disorders (ROR = 7.31, 95% CI = 7.16-7.47) and Endocrine disorders (ROR = 4.09, 95% CI = 3.83-4.37), the latter representing unlabeled findings. In addition, we detected previously unlisted AEs, including colitis, oral lesions, immune-mediated pancreatitis, pulmonary toxicity, lung consolidation and tubulointerstitial nephritis. Sex stratification revealed male predominance in respiratory toxicity vs. female predisposition to renal injury. A bimodal time-to-onset distribution was observed: 52.57% of AEs occurred within 0-30 days post-treatment, with a secondary peak (6.63%) at 181-360 days. This large pharmacovigilance study identifies signals of disproportionate reporting (SDRs) consistent with pemetrexed's established toxicities (e.g., myelosuppression, nephrotoxicity) and detects additional unlabeled safety signals, particularly immune-mediated endocrine, renal, and dermatologic manifestations. The bimodal onset pattern of these SDRs highlights clinically relevant monitoring windows, and observed sex- and age-related differences in SDR reporting suggest a need for individualized risk mitigation. These findings underscore the importance of vigilant surveillance for potential immune-mediated toxicities and adherence to vitamin supplementation protocols to manage hematologic risk. Prospective studies are needed to validate these reporting associations and clarify potential causality for these novel signals.

Frozen shoulder (FS) is a chronic and painful joint disorder characterized by progressive stiffness and functional limitation. Its multifactorial pathophysiology remains poorly understood, although emerging evidence suggests a role for low-grade inflammation, metabolic dysregulation, and immune-endocrine imbalance. Nutrition and lifestyle factors may therefore represent modifiable contributors to disease development and progression. This cross-sectional observational study investigated the association between dietary profile, physical activity, pain intensity, and shoulder function in 57 patients with FS (44 women and 13 men). Sociodemographic variables, physical activity levels, adherence to the Mediterranean diet, detailed dietary intake, and shoulder pain and disability were assessed using validated instruments. Multivariate analyses, including Elastic Net and sparse partial least squares regression, were used to identify dietary and lifestyle predictors of pain and functional impairment. Higher consumption of refined carbohydrates, starch, total cholesterol, and processed animal products was associated with worse shoulder function. In contrast, greater intake of specific micronutrients, including thiamine, niacin, iron, manganese, and vitamin D, as well as decaffeinated coffee and higher physical activity levels, was associated with lower pain and disability, particularly in women. Sex-stratified analyses showed stronger and more consistent associations between micronutrient intake and clinical outcomes in women, while predictive modeling in men was limited by sample size. These findings suggest the presence of a nutritional pattern associated with symptom severity in FS, supporting a potential immunometabolic contribution to the condition. However, due to the cross-sectional design, causal relationships cannot be established and reverse causation remains possible. These results should be interpreted as hypothesis-generating and highlight the need for longitudinal and interventional studies to determine whether dietary and lifestyle modifications can influence clinical outcomes.

To summarize the clinical features, risk factors, and maternal and fetal outcomes of spontaneous complete uterine rupture during the second and third trimester of pregnancy, and to explore key aspects of early identification and management, especially in cases without prior cesarean section. This study aims to provide evidence-based insights for early warning and emergency intervention in clinical practice. This is a retrospective case series analysis of seven cases of spontaneous complete uterine rupture occurring in the second and third trimester of pregnancy. We analyzed patient demographics, obstetric history, gestational age at rupture, clinical presentation, management strategies, and outcomes. Descriptive statistical methods were employed, with continuous variables expressed as medians (range) and categorical variables as frequencies (percentages). The median age of the seven women was 30 years old, with a median gestational age at rupture of 27 weeks. Among them, 57.1% (4/7) experienced rupture in the second trimester (<28 weeks), and 71.4% (5/7) had non-labor ruptures. 42.9% (3/7) of the cases involved women without a previous cesarean section. The most common clinical symptom was sudden onset of abdominal pain, often accompanied by shoulder pain, abnormal fetal heart rate, or vaginal bleeding, though these symptoms were non-specific. Surgical confirmation revealed rupture sites in the lower uterine segment (3 cases), fundus (3 cases), and cornua (1 case). Hemorrhagic shock (blood loss &#x2265; 2000 mL) occurred in 85.7% (6/7) of cases, with three cases complicated by placenta accreta spectrum (PAS). While all mothers survived, the perinatal mortality rate was 85.7% (6/7), with only one surviving fetus. Spontaneous complete uterine rupture during the second and third trimester of pregnancy typically presents as non-labor acute abdominal pain and may occur in women without a prior uterine surgery history, especially in the second trimester, where fetal outcomes are poor. Clinicians should maintain a high index of suspicion for uterine rupture in pregnant women presenting with acute abdominal pain, regardless of previous cesarean history. Early diagnosis and the establishment of a rapid, multidisciplinary emergency response are critical to improving maternal and fetal outcomes.

Systemic sclerosis (SSc) exhibits heterogeneous pulmonary involvement, most commonly interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). How systemic inflammatory, immune, and nutritional states differ across these lung phenotypes remains incompletely understood. To characterize integrated inflammatory-immune-nutritional signatures across SSc lung phenotypes and validate their robustness using multivariable modeling and unsupervised clustering. We conducted a retrospective cross-sectional study of 314 consecutive SSc inpatients fulfilling the 2013 ACR/EULAR criteria (2018-2023). Patients were stratified into four lung phenotypes: ILD-/PAH- (n = 45), ILD + /PAH- (n = 183), ILD-/PAH + (n = 12), and ILD + /PAH + (n = 74). Routine laboratory data were used to derive inflammatory markers (hs-CRP, ESR, NLR, PLR, MLR, SII, SIRI, SCI), nutritional parameters (BMI, albumin, lipid profiles), and immune markers (autoantibodies, immunoglobulins, complement). We performed (1) group comparisons; (2) multinomial logistic regression focusing on the three predominant phenotypes (ILD-/PAH- as reference; ILD + /PAH-; ILD + /PAH +), excluding ILD-/PAH + due to small sample size (n = 12) and sparse-data instability; and (3) k-means clustering of standardized biomarker profiles. Internal validation and clustering stability analyses were performed. ILD + /PAH + patients showed a higher systemic inflammatory burden, including higher ESR (38 [21-61.5] vs. 23 [10-45] mm/h, p = 0.008), hs-CRP (10.15 [3.34-28.18] vs. 5.9 [1.5-16.1] mg/L, p = 0.017), CRP/albumin ratio (0.33 [0.11-0.95] vs. 0.17 [0.04-0.49], p = 0.019), and SII (1124.76 [700.8-2034.14] vs. 820.34 [461.33-1197.08], p = 0.013) compared with ILD-/PAH-. Anti-Scl-70 positivity was enriched in ILD-containing phenotypes (p < 0.001), and immunoglobulins varied (IgG p = 0.032; IgA p = 0.028). In multinomial models, female sex and longer disease duration were associated with both ILD + /PAH- (OR 3.48, 95%CI 1.51-8.04; OR 1.02 per month, 95%CI 1.01-1.04) and ILD + /PAH + (OR 3.49, 95%CI 1.31-9.33; OR 1.03 per month, 95%CI 1.01-1.05). Triglycerides (Z-score) were associated with ILD + /PAH- (OR 1.70, 95%CI 1.05-2.77), while log(ESR) (Z-score) was associated with ILD + /PAH + (OR 1.82, 95%CI 1.01-3.27). Clustering supported a three-cluster structure driven by inflammation (ESR), mucosal immunity (IgA), and metabolic dysregulation (triglycerides), with strong stability (Adjusted Rand Index = 1.00). Internal validation showed stable within-cohort performance (accuracy &#x223c;0.62-0.65). SSc lung phenotypes defined by ILD/PAH co-occurrence display distinct integrated inflammatory-immune-nutritional signatures. The ILD + /PAH + phenotype reflects a high-burden systemic inflammatory state, and a small set of coherent markers (ESR, triglycerides, IgA, and autoantibodies) provides a reproducible framework for phenotype-oriented stratification.

Critically ill patients experience high rates of thromboembolic and bleeding events despite the use of pharmacological thromboprophylaxis or weight-based anticoagulation. Laboratory assays for drug monitoring, as Anti-factor Xa (Anti-Xa), overcome the limitations of activated partial thromboplastin time (aPTT) but only quantify drug effects and do not reflect global haemostasis. Viscoelastic testing (VET) may provide additional functional information. Robust clinical data in the ICU setting are limited. Primary objective is to assess the association between VET clotting time (CT) in Russell viper venom (RVV) assay and Anti-Xa activity. Secondary objectives include assessing whether VET or Anti-Xa aligns more closely with global haemostatic function, defined by thrombin generation assay (TGA) variables. Exploratory analyses aim to characterise associations among VET parameters, standard laboratory tests, and biomarkers; model dose-exposure-response relationships; and identify clinical modifiers as sepsis or renal dysfunction. Sepsis status will be incorporated as predefined effect modifier in mixed-effects models. This single-center, prospective, observational cohort study enrols critically ill adults receiving unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Sampling is standardized to pharmacokinetics: 4&#x202f;h post-dose for subcutaneous LMWH and 4-6&#x202f;h post-start for i.v. UFH. At each time point, Anti-Xa, VET on ClotPro&#xae; (RVV, EX, and RVH assays), standard laboratory tests, and advanced haemostatic markers (factor VIII, factor XIII, PF1&#x202f;+&#x202f;2, TGA, PAP, PAI, TFPI, TAT) are collected. Two repeated measurements per patient capture intra-individual variability. We hypothesize that CT-RVV demonstrates a clinically interpretable monotonic relationship with Anti-Xa activity under ICU conditions. We further anticipate discordance between Anti-Xa and global haemostatic markers in a relevant subset of patients, particularly in sepsis, supporting the hypothesis that VET aligns more closely with functional haemostasis than Anti-Xa alone. These findings are expected to delineate when fixed dosing is insufficient, identify predictors of under- or over-anticoagulation, and guide personalised anticoagulation strategies. If RVV-CT consistently correlates with Anti-Xa across clinical states, VET could streamline monitoring where laboratory turnaround time limits timely dose adjustment; if not, the results will clarify the boundaries of VET applicability and highlight scenarios requiring laboratory confirmation or TGA. Ethics approval was obtained from the responsible committee of Technical University Dresden (BO-EK-338082024). The study is registered with the German Clinical Trials Register (DRKS00037385), registration date: 10 July 2025, https://drks.de/search/de/trial/DRKS00037385.

Burn wound infections (BWIs) represent a major cause of morbidity and mortality among hospitalized burn patients. Pseudomonas aeruginosa is recognized for its ability to acquire multidrug resistance (MDR) and form biofilms that enhance virulence and antimicrobial tolerance. This study investigated the association between biofilm formation and multidrug resistance among P. aeruginosa isolates from burn wound infections in Sana'a City, Yemen. A cross-sectional study was conducted at Republic Hospital, Sana'a City, Yemen, from October 2023 to December 2024. A total of 424 burn wound samples were collected and processed using standard microbiological techniques. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines (CLSI, 2022). Biofilm production was assessed by the microtiter plate method, and polymerase chain reaction (PCR) was used to detect biofilm-associated genes (algD, pslD, and pelF). Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) version 26.0, with p&#x202f;&#x2264;&#x202f;0.05 considered significant. Of 424 burn wound samples, P. aeruginosa was the predominant isolate (39.6%), followed by Klebsiella pneumoniae (27.1%) and Staphylococcus aureus (19.3%). Significant risk factors associated with bacterial isolation included prior antibiotic use (&#x3c7; 2&#x202f;=&#x202f;16.4, p&#x202f;=&#x202f;0.001), wound debridement (&#x3c7; 2&#x202f;=&#x202f;21.6, p&#x202f;=&#x202f;0.001), and surgical skin grafting (&#x3c7; 2&#x202f;=&#x202f;11.7, p&#x202f;=&#x202f;0.001). P. aeruginosa showed high resistance to ceftazidime (89.8%), cefepime (90.4%), ticarcillin (92.2%), and meropenem (61.9%), while remaining largely sensitive to colistin (97%). Among isolates, 13% were MDR, 21% extensively drug-resistant (XDR), and 51% pan-drug-resistant (PDR) strains. Biofilm formation was observed in 66.4% of P. aeruginosa isolates-19.7% strong, 47.0% moderate, and 33.3% non-producers. The biofilm-associated genes algD, pslD, and pelF were detected in 38, 35, and 27% of isolates, respectively. A significant association was observed between strong biofilm formation and the presence of the pslD gene (&#x3c7; 2&#x202f;=&#x202f;4.8, p&#x202f;=&#x202f;0.03), but not with MDR status (p&#x202f;>&#x202f;0.05). P. aeruginosa remains the leading cause of burn wound infections in Sana'a City, Yemen, exhibiting alarmingly high levels of carbapenem and cephalosporin resistance. Although biofilm formation was common, no significant association was found between biofilm production and multidrug resistance. The high prevalence of PDR strains underscores the urgent need for antimicrobial stewardship, routine susceptibility testing, and infection control measures in burn centers.

Genetic variants in TOLLIP and MUC5B influence innate immune signaling and mucosal defense and have been implicated in interstitial lung disease (ILD) susceptibility. However, data from Indian populations remain scarce. This study aimed to characterize single nucleotide polymorphisms (SNPs) in TOLLIP and MUC5B among patients with interstitial lung disease (ILD) and its subtypes. Additionally, it investigated the relationship between these genetic variants and inflammatory biomarkers, as well as the patterns of linkage disequilibrium (LD) in patients with ILD from Western India. This cross-sectional study enrolled 200 patients with ILD and 104 healthy controls. Six SNPs, TOLLIP rs3750920, rs111521887, rs5743890, rs5743894, rs5743854, and MUC5B rs35705950, were genotyped using Sanger sequencing and PCR-RFLP. Serum cytokine levels (IL-1&#x3b2;, TNF-&#x3b1;, IFN-&#x3b3;, and IL-6) were measured using a multiplex bead-based immunoassay. LD was assessed using Haploview software. Connective tissue disease-related ILD (CTD-ILD) was the most common subtype (45%). The TOLLIP rs3750920_T allele was significantly more frequent in idiopathic pulmonary fibrosis (IPF) than in controls (66.1% vs. 50.5%; p&#x202f;=&#x202f;0.038). The TOLLIP rs111521887_G allele was more frequent in CTD-ILD than controls (18.4% vs. 7.4%; p&#x202f;=&#x202f;0.002). The TOLLIP rs5743890_C allele was more frequent in controls than ILD (7.5% vs. 2.9%; p&#x202f;=&#x202f;0.016). The TOLLIP rs5743894_C allele was more frequent in all patients with ILD than in controls (14.5% vs. 8.1%; p&#x202f;=&#x202f;0.03), and specifically in the IPF subtype (19.2% vs. 8.1%; p&#x202f;=&#x202f;0.01). The TOLLIP rs5743854_G allele was found to be more frequent in the idiopathic NSIP subtype as compared to controls (41.2% vs. 23.2%; p&#x202f;=&#x202f;0.033). The MUC5B rs35705950_T allele was significantly more frequent in ILD than controls (19.6% vs. 5.8%; p&#x202f;=&#x202f;0.0008). Among cytokines, IFN-&#x3b3; was significantly elevated in TOLLIP rs5743854 C/C and MUC5B rs35705950 G/G homozygous genotypes in patients with ILD. Furthermore, LD analysis revealed no significant haplotype blocks in this population. This study provided the first population-specific data on TOLLIP and MUC5B genotypes in Indian patients with ILD, highlighting genotype-driven variation in IFN-&#x3b3; and distinct allele-frequency patterns compared to Western cohorts. This study also indicated that one-third of the Indian patients with ILD, higher than the 6-7% from currently available Asian data, had genotypes that may benefit from NAC therapy.

Metabolic dysfunction-associated fatty liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), has become the most common chronic liver disease worldwide. Although excessive lipid accumulation, insulin resistance, and chronic low-grade inflammation are recognized as the main pathophysiological drivers, an increasing body of research indicates that the relationship between circadian rhythms, gut microbiota, and liver metabolism is far more complex than previously imagined, forming a systemic regulatory network. Disruption of circadian rhythms can affect the temporal coordination of metabolic pathways in the liver and other surrounding tissues. At the same time, the gut microbiota itself also exhibits circadian rhythm variations. The dysregulation of these rhythms, leading to microbial imbalance, intestinal permeability defects, and imbalances in microbial metabolites, can exacerbate lipid deposition and inflammatory responses in the liver. Research shows that important microorganisms can produce short-chain fatty acids, regulate bile acid balance, and enhance intestinal barrier function, creating a synergistic effect with the host's circadian rhythms. Conversely, during circadian disruption, the proliferation of harmful symbionts can exacerbate the entry of lipopolysaccharides into the bloodstream, oxidative stress, and the development of steatohepatitis. This relationship among the three establishes the ' circadian rhythm-gut microbiota-liver axis' as a new model for understanding the mechanisms underlying MASLD and for developing temporal therapies and microbiome interventions. This review systematically explores how circadian rhythms regulate the relationship between the gut microbial ecology and liver metabolism, focusing on the microbial species closely related to the interaction between circadian rhythms and MASLD. It also introduces emerging therapeutic strategies, including time-restricted feeding, circadian probiotics, postbiotics supplementation, and circadian rhythm drugs. These findings collectively suggest that targeting the temporal dimension of the interactions between the host and microbiota holds clinical potential for the prevention and treatment of MASLD.

Polycystic ovary syndrome (PCOS) is associated with a high prevalence of obstructive sleep apnea (OSA); however, its impact on the clinical manifestations of PCOS remains unclear. This study aimed to investigate the clinical characteristics, reproductive endocrine profiles, and glucose-lipid metabolic features in women with PCOS complicated by OSA and to evaluate their potential implications for pregnancy outcomes. A total of 294 infertile women with PCOS treated at Heze Municipal Hospital between February 2023 and December 2024 were enrolled after excluding ineligible participants. Clinical characteristics and reproductive endocrine and metabolic parameters were collected, and factors associated with OSA in women with PCOS were analyzed using the univariate analysis and the logistic regression analysis. Additionally, 101 women with PCOS and OSA were randomly assigned to either a lifestyle intervention control group or a lifestyle intervention and continuous positive airway pressure (CPAP) group, and changes in hormonal and metabolic parameters as well as pregnancy outcomes were evaluated. The prevalence of OSA in women with PCOS was 34.4%, of whom 10.9% had moderate to severe OSA. Higher body mass index, hyperinsulinemia, elevated triglycerides (TGs), and reduced anti-M&#xfc;llerian hormone (AMH) levels were independently associated with an increased risk of OSA in women with PCOS. Compared with the control group, the CPAP treatment group exhibited significant reductions in serum testosterone (T), insulin (INS), and triglyceride (TG) levels, along with a significantly higher clinical pregnancy rate (p&#x202f;<&#x202f;0.05). Infertile women with PCOS and OSA exhibit significant disturbances in reproductive endocrine and glucose-lipid metabolism. CPAP therapy may improve these metabolic abnormalities, and when combined with ovulation induction and assisted reproduction, it may lead to better pregnancy outcomes, highlighting the potential benefit of early screening and intervention for OSA in women with PCOS.

Enterobius vermicularis, commonly known as the pinworm, is a prevalent intestinal nematode, particularly affecting children worldwide. Although infection is often asymptomatic, it may occasionally lead to complications, including appendiceal involvement. The role of E. vermicularis in the pathogenesis of acute appendicitis remains controversial and is frequently overlooked. We report a case of a 10-year-old child who presented with intermittent right lower quadrant abdominal pain without fever or systemic symptoms. Initial ultrasound revealed small mesenteric lymph nodes, with no clear evidence of appendiceal pathology. Empirical treatment with antibiotics and anti-inflammatory agents failed to relieve the symptoms. A follow-up ultrasound demonstrated a thickened retrocecal appendix with hypoechoic intraluminal content. Due to persistent pain, a laparoscopic appendectomy was performed, revealing a white, non-segmented roundworm within the appendiceal lumen. Histopathological examination and direct microscopic analysis confirmed follicular appendicitis with intraluminal nematodes morphologically consistent with E. vermicularis. Postoperative parasitological examination further supported the diagnosis, with detection of characteristic eggs using the Scotch tape test, while stool examinations remained negative. These findings suggested E. vermicularis as the most likely etiological agent and supported its pathogenic role in the patient's clinical presentation. The patient was treated with albendazole, followed by a second dose 2 weeks later. Simultaneous treatment was administered to household contacts, and strict hygiene measures were recommended to prevent reinfection. Clinical recovery was complete, with no postoperative complications. This case highlights the importance of considering parasitic infections in the differential diagnosis of acute abdominal pain, even in the absence of systemic inflammatory markers, particularly in endemic or underrecognized settings. Early recognition and targeted therapy are essential to prevent recurrence and intra-familial transmission.

Waldenstr&#xf6;m macroglobulinemia (WM) is a rare CD20-positive B-cell non-Hodgkin lymphoma. It is characterized by lymphoplasmacytic infiltration in the bone marrow and abnormal monoclonal IgM secretion. WM complicated by renal amyloidosis is uncommon but associated with rapid progression of organ damage. Accurate identification of pathogenic factors and individualized treatments are essential to improve prognosis. This paper reports the case of a 75-year-old female who initially presented with facial edema and bilateral lower-extremity edema lasting 2&#x202f;days. Additional symptoms included foamy urine, frequent urination, and urgency. Laboratory tests revealed significant proteinuria (24-h urinary protein, 6.11&#x202f;g), hypoalbuminemia (serum albumin, 20.07&#x202f;g/L), and impaired renal function (serum creatinine, 129.90&#x202f;&#x3bc;mol/L; eGFR, 45.2&#x202f;mL/min/1.73&#x202f;m2). Immunofixation electrophoresis detected monoclonal IgM-&#x3bb; immunoglobulin in both serum and urine. Bone marrow biopsy demonstrated clonal lymphoplasmacytic infiltration (32%), and genetic testing revealed a positive MYD88-L265P mutation (mutation frequency, 28.5%). Renal biopsy indicated diffuse deposition of &#x3bb; light chains predominantly in the glomerular mesangium. Ultrastructural examination revealed amyloid fibrils, confirming the diagnosis of AL &#x3bb;&#x202f;-&#x202f;type amyloid nephropathy. Chemotherapy with rituximab, cyclophosphamide, and dexamethasone (RCD regimen), combined with symptomatic supportive therapy, resulted in temporary improvement of clinical symptoms and laboratory parameters. However, the disease progressed rapidly. The patient died on Jan 28, 2024, approximately 3&#x202f;months after discharge, due to multiple organ failure involving cardiac, renal, and respiratory dysfunction. Based on relevant literature and the Chinese Expert Consensus on Diagnosis and Treatment of Lymphoplasmacytic Lymphoma (LPL)/WM (2022 Edition) [Abstract 3], this paper discusses diagnostic criteria, differentiation of pathogenic components, treatment strategies, and prognostic factors. These findings may provide clinical guidance for similar rare cases.