搜索结果：Journal of inflammation research

Sickle cell disease (SCD) is a severe, inherited hemoglobin disorder characterized by chronic hemolysis, vaso-occlusive crises (VOCs), and systemic inflammation. Hydroxyurea is the standard conventional pharmacotherapy for SCD, but it has certain limitations, necessitating the need to explore other safe and effective treatment options for SCD. Ayurveda interventions offer a potential therapeutic approach complementary to conventional medicine for SCD management, with anti-inflammatory, immunomodulatory, and hematopoietic properties. This randomized controlled trial will evaluate the efficacy and safety of an Ayurvedic therapeutic regimen as an adjunct to hydroxyurea in SCD management, assessing its impact on hematological parameters, inflammatory biomarkers, VOC frequency, and overall quality of life. A PROBE (Prospective, Randomized, Open-Label, Blinded End Point) study will be conducted on individuals of any gender aged 18 years or older and diagnosed with SCD (with hemoglobin S levels more than 60% and a history of at least 1 VOC per year over the past 3 y). Individuals with acute VOC or any severe infection requiring hospitalization, a history of significant comorbidities, or hematopoietic stem cell transplantation will not be considered. The study will be conducted at the All India Institute of Medical Sciences, Bhopal, India. A total of 100 participants will undergo random assignment in a 1:1 ratio to receive either an Ayurveda regimen (Dadimadi Ghrita, Punarnavadi Mandura, and Vasaguduchyadi Kwatha) as an add-on to hydroxyurea or hydroxyurea alone for 8 months. The primary outcome will be a change in hemoglobin electrophoresis parameters (hemoglobin S, fetal hemoglobin, and adult hemoglobin) and the frequency of VOC episodes over 8 months. The secondary outcome measures include changes in the levels of proinflammatory markers (interleukin-6, interleukin-8, C-reactive protein, and transforming growth factor-β) and lactate dehydrogenase, frequency of hospitalization for VOCs and blood transfusions, and health-related quality of life (Short Form-8 Health Survey questionnaire). Safety will be evaluated by recording the incidence of adverse events and changes in liver and kidney function tests from baseline. The recruitment of study participants was initiated on November 1, 2023. By the second week of February 2025, 83 participants had been enrolled in the study. The final study is expected to be complete by December 31, 2025. We will start the analysis of the study outcomes in February 2026, and the publication of the final results is expected by August 2026. This randomized controlled trial protocol outlines a rigorous study design aimed to explore the potential benefits of an integrated therapeutic regimen comprising Ayurveda interventions and standard conventional care in the long-term management of SCD through validated clinical and laboratory parameters. The outcomes of this study can address the needs and challenges associated with SCD management and inform future management protocols.

Deficiency of adenosine deaminase 2 (DADA2) is caused by mutations in the ADA2 gene and results in an auto-inflammatory state. Hepatosplenomegaly, with or without abnormalities in liver enzymes, has been reported in DADA2. Anti-tumour necrosis factor (anti-TNF) therapy is the standard of care for the prevention of recurrent ischemic strokes and reduction of inflammatory burden. However, little is known about the extent of hepatic involvement and the utility of non-invasive tools for identifying liver disease and monitoring treatment response. Retrospective analysis was performed on a prospective cohort of 70 patients with DADA2. Patients underwent baseline and annual laboratory testing, abdominal imaging and transient elastography. Hepatomegaly and splenomegaly were assessed on imaging, with splenomegaly defined using the spleen-to-height (SH) ratio. Liver biopsy and esophagogastroduodenoscopy were performed when indicated. At baseline, elevated ALT was uncommon (29%). Hepatomegaly and splenomegaly were present in 36% and 58%, respectively. Liver biopsies were performed in 12 patients, 8 of whom showed porto-sinusoidal vascular disease (PSVD). Over a median follow-up of 4.5 years, 40% demonstrated persistently elevated ALT levels. Clinically evident portal hypertension was present in 14%, and decompensation events, such as ascites and variceal bleeding, occurred in 5%. Anti-TNF therapy resulted in resolution of splenomegaly in 28% and a reduction in mean SH ratio across the entire cohort. Patients who underwent haematopoietic cell transplantation (HCT) appeared to be at risk for complications such as hepatic graft versus host disease and veno-occlusive disease. DADA2 vasculopathy appears to affect intrahepatic portal veins and result in PSVD. SH ratio shows significant promise in identifying liver involvement and monitoring treatment response. The improvement in SH suggests that PSVD may be reversible with treatment in this setting. Hepatic evaluation at baseline is encouraged for all patients, and pre-HCT liver biopsy should be considered, as there can be clinically silent liver disease that could potentially cause transplant-related complications. Deficiency of adenosine deaminase 2 (DADA2) is a rare genetic condition that causes inflammation and can affect multiple organs. We studied how often the liver is involved in DADA2 and whether simple, noninvasive tests can help detect liver involvement and track response to treatment. We found that DADA2 can cause problems with tiny blood vessels inside the liver called porto‐sinusoidal vascular disease (PSVD). PSVD can increase pressure in the portal vein system (portal hypertension), which may cause enlargement of the spleen, low platelet counts, development of enlarged veins in the oesophagus (varices), and fluid accumulation in the abdomen (ascites). In our cohort, clinical signs of portal hypertension were documented in 14% of patients, and 5% developed complications such as bleeding from varices or ascites. Because liver disease was largely silent, we evaluated practical ways to identify it early. More than half of patients had an enlarged spleen at baseline, and spleen size adjusted for height (the spleen‐to‐height ratio) emerged as a sensitive marker of liver involvement. Treatment with anti‐tumour necrosis factor medications led to a reduction in the spleen‐to‐height ratio in most treated patients, suggesting improvement in liver disease. We recommend routine screening for liver involvement in DADA2, with SH ratio and platelet counts, selective liver biopsy and endoscopy for suspected portal hypertension, and baseline hepatology evaluation prior to stem cell transplantation.

BackgroundEndometriosis is a hormone-driven systemic inflammatory condition characterized by endometrial-like lesions which grow throughout the body affecting up to 15% of women worldwide with symptoms including chronic pain, infertility, and persistent fatigue. Many patients report a reduction in their quality of life, potentially driven in part by poor sleep quality. Despite this low sleep quality is not a commonly recognized symptom of endometriosis.ObjectiveWe aimed to examine the association between endometriosis and poor sleep quality.DesignWe conducted a systematic literature review and mixed-effects meta-analysis to evaluate the association between endometriosis and sleep quality.Data sources and methodsSix studies identified through PubMed and Embase met inclusion criteria and were assessed for quality. Between-group standardized mean differences (SMD) were pooled, and sensitivity analyses and meta-regressions were performed to evaluate the influence of between-study heterogeneity.ResultsPooling of all studies produced a standardized mean difference of 0.69 (95% CI: 0.28,1.09) with high heterogeneity (I2 = 94% p<0.01), which equates to a 2.44 (95%CI: 0.99; 3.85) point increase on the Pittsburg Sleep Quality Index (indicating poorer overall sleep quality) for endometriosis patients compared to healthy controls. This association persisted during sensitivity analyses.ConclusionThis observed association may be driven by a pain-sleep quality feedback loop or by the inflammation and hormonal imbalances of endometriosis. While there are several limitations to interpreting these results, including differences in control selections and adjustments for potential confounders between included studies, it is the first quantitative evaluation of the association between endometriosis and poor sleep quality across populations. Since sleep quality predicts chronic pain patterns, future research and patient treatment plans should focus on potential interventions to improve the sleep quality of endometriosis patients experience to reduce the societal and personal burdens of this disease. Endometriosis is a chronic condition where tissue similar to the lining of the uterus grows outside of it, most often in the abdomen. It affects as many as one in seven women worldwide and can cause severe pain, fatigue, and infertility. Many people living with endometriosis also report problems with sleep, but poor sleep is not widely recognized as one of the condition&#x2019;s symptoms or routinely studied by researchers. To better understand whether people with endometriosis experience worse sleep than those without the condition, we reviewed and combined the results of previous scientific studies that measured sleep quality in both groups. This process, called a systematic review and meta-analysis, helps summarize evidence from multiple studies to reach stronger conclusions. We identified six high-quality studies that met our inclusion criteria. When we analyzed them together, we found that people with endometriosis had significantly poorer sleep quality than those without it. On average, their scores on a standard sleep measure, the Pittsburgh Sleep Quality Index, were about 2.4 points higher, indicating worse overall sleep quality. This difference was consistent across several types of analyses, even though the studies varied in design and population. Our findings suggest that endometriosis may affect sleep through ongoing pain, inflammation, and hormonal changes, which can in turn worsen pain and fatigue, a cycle that may amplify the overall burden of the disease. Because good sleep is essential for physical and emotional well-being, these results highlight the need for more research on how endometriosis disrupts sleep and how improving sleep might reduce pain and improve quality of life for patients. Recognizing poor sleep as a common and meaningful symptom could lead to more holistic care for people living with endometriosis.

Coronary heart disease (CHD) is one of the most prevalent cardiovascular pathologies, with complications significantly increasing mortality rates. The pathogenesis of CHD is complex and multidimensional, and its cellular and molecular basis remains incompletely understood. Recent studies indicate that multiple forms of cell death participate in the initiation and progression of CHD, including inflammation-driven factors (Pyroptosis- Necroptosis- Ferroptosis), context-dependent modulators (Apoptosis- Autophagy), and emerging/hypothetical mechanisms (PANoptosis- Cuproptosis- Disulfidptosis). Meanwhile, traditional Chinese medicine (TCM) is gaining increasing attention in the management of cardiovascular diseases, particularly CHD. This research summarizes the roles of multiple cell death pathways in the pathogenesis of CHD and provides a detailed review and comprehensive analysis of the mechanisms underlying existing experimental studies on TCM formulas and active components used to treat CHD. We highlight representative TCM metabolites and TCM formulas, such as resveratrol, TongMai YangXin Wan, Gualoupi Injection, etc. It concludes that TCM counteracts CHD by inhibiting various cell death pathways. Current basic research primarily focuses on signaling pathways such as PI3K/Akt, TNF, and MAPK. This work provides new insights and approaches for the treatment of CHD and further research. Finally, it identifies current challenges, including unclear compositions of TCM and insufficient validation of mechanisms, and proposes new directions for future research.

Traumatic brain injury (TBI) triggers profound neuroinflammatory responses; however, the regulatory role of small nucleolar RNAs (snoRNAs) in TBI-associated neuroinflammation remains poorly understood. This study evaluated its prognostic value in TBI. A controlled cortical impact (CCI) model was established in male C57BL/6 mice and validated through modified neurological severity scoring (mNSS), hematoxylin-eosin (H&E) staining, and immunostaining for IgG leakage and Nissl substance. Cortical snoRNA expression profiles were assessed using microarray analysis, with differentially expressed candidates confirmed by quantitative real-time PCR (qRT-PCR). The spatial distribution of snoRNAs was determined via fluorescence in situ hybridization (FISH), while the anti-inflammatory effects of snoRNA Gm24418 were evaluated in vivo and vitro. Downstream molecular pathways were identified through transcriptomic sequencing combined with bioinformatics analysis. Mice subjected to CCI exhibited significant motor and cognitive impairments (elevated mNSS), neuronal loss (as indicated by H&E and Nissl staining), and blood-brain barrier disruption (evidenced by IgG extravasation). Microarray analysis identified 47 dysregulated small nucleolar RNAs (snoRNAs), comprising 43 that were downregulated and 4 that were upregulated, with Gm24418 exhibiting the most significant downregulation. FISH confirmed the localization of Gm24418 predominantly in cortical neurons. Overexpression of Gm24418 in N2A cells and mice significantly reduced the levels of pro-inflammatory cytokines, including IL-1&#x3b2;, TNF-&#x3b1;, and IL-6, and suppressed the activation of Ccl2 and TNF signaling pathways. Mechanistic analyses indicated that Gm24418 overexpression is associated with downregulation of the TNF signaling pathway, thereby attenuating neuroinflammation and promoting the restoration of blood-brain barrier integrity following TBI. Gm24418 is identified as a neuron-specific snoRNA that ameliorates TBI-induced neuropathology through influencing the expression of key inflammatory mediators, including CCL2 and TNF-&#x3b1;, representing a promising novel therapeutic target for post-traumatic neuroinflammation.

Bronchiectasis (BE) is a chronic respiratory disease characterized by damage to the bronchial wall structure and permanent dilation of the bronchi. The symptoms include a persistent cough, excessive production of purulent sputum, and recurrent hemoptysis. Dysbiosis of the microbiome plays a crucial role in the progression of BE. An increased abundance of pathogenic bacteria, along with viral and fungal infections, is closely associated with disease severity and clinical outcomes. Next-generation sequencing technology has significantly enhanced the sensitivity and resolution of the airway microbiome, providing powerful tools for a more detailed characterization of the microecology of BE. However, certain challenges still exist in clinical applications of this technology. In addition, extra-airway microbiomes, such as the gut and oral microbiome, may participate in airway inflammation and immune regulation through the gut-lung axis and oral-lung axis. In this review, we summarize the characteristics of microbiome dysbiosis in BE and highlight the potential value of related biomarkers in disease classification, severity assessment, and prognosis. We also provide an overview of recent treatment advancements. A deeper understanding of the microbiome's role in BE may facilitate early diagnosis and the optimization of individualized treatment strategies. Microbiome and its role in bronchiectasisThe microbiome refers to the collection of microorganisms, including bacteria, fungi, viruses, and other microbes. A healthy microbiome is essential for overall well-being, as it plays a crucial role in protecting against infections and supporting bodily functions. However, this balance can be disrupted by various diseases. Dysbiosis of the microbiome plays a significant role in the progression of BE, characterized by reduced microbial diversity and increased abundance of pathogenic bacteria. In this review, we summarize how the microbiome interacts with the immune system and influences disease severity. It also highlights emerging biomarkers and new therapies, including DPP-1 inhibitors, inhaled antibiotics, biologics that target specific immune pathways, and innovative approaches like phage therapy. However, research on extra-airway microbiomes is still limited. Furthermore, variations across different regions and populations make it challenging to apply findings universally. A better understanding of the microbiome could lead to more accurate diagnoses, personalized treatments, and ultimately better long-term outcomes for patients.

We performed a single-center observational cohort study on patients with COVID-19. We retrospectively analyzed 54 patients with confirmed SARS-CoV-2 infection, diagnosed as critically ill. Severely ill patients have a poor prognosis and it is a matter of great interest to identify these cases for an adequate management. Current findings revealed that altered levels of some blood markers might be linked with the degree of severity and mortality of patients with COVID-19. Our study aimed to assess the relationship between inflammation and coagulation in SARS-CoV-2 infection and to find out if pro-inflammatory markers are correlated with coagulation parameters in COVID-19. Pro-inflammatory markers included leptin and classical biomarkers. This paper highlights the results obtained. We found statistically significant associations between blood levels of various biomarkers including leptin, IL-6, ferritin, neutrophil-lymphocyte ratio, C-reactive protein, fibrinogen, erythrocyte sedimentation rate and lactate dehydrogenase and the presence of coagulopathy, as indicated by the Pearson Chi-Square and Likelihood Ratio tests. The relationships are not linear, as indicated by the nonsignificant Linear-by-Linear Association test. The correlations between some biomarkers such as leptin, IL-6, ferritin, neutrophil-lymphocyte ratio, C-reactive protein, fibrinogen, erythrocyte sedimentation rate and lactate dehydrogenase and coagulopathy are weak and not statistically significant and the correlation between IL-6 levels and coagulopathy is very weak and negative and not statistically significant. Different crosstabulations between serum leptin levels and D-dimers, Prothrombin time, Prothrombin activity, International-normalized-ratio and activated partial thromboplastin time have been performed including the analysis of a potentional correlation. There are statistically significant associations between serum leptin levels and coagulation parameters, including D-dimers, prothrombin time, prothrombin activity and activated partial thromboplastin time, as indicated by the Pearson Chi-Square test. There is also a statistically significant association between serum leptin levels and international-normalized ratio (INR) as indicated by the Pearson Chi-Square test. The Linear-by-Linear Association test indicates a significant linear relationship between Leptin levels and international-normalized ratio. Pearson R shows a moderate positive correlation, which is statistically significant.

Colitis-associated colorectal cancer (CAC) is the most severe complication of inflammatory bowel disease (IBD), characterized by multifocal lesions and poor prognosis. Aberrant lipid metabolism drives CAC progression by modulating the tumor microenvironment, activating oncogenic pathways, and facilitating immune escape. These metabolic alterations supply energy for tumor cells, disrupt the homeostasis of the tumor microenvironment, and contribute to gut microbiota dysbiosis, ultimately establishing a vicious cycle of "metabolism-inflammation-carcinogenesis." Although the role of lipid metabolism in sporadic colorectal cancer has been extensively studied, the specific metabolic rewiring that triggers the malignant switch during chronic colitis remains systematically unexplored. From the viewpoint of the dynamic transition toward malignancy, this review dissects the synergistic interactions between lipid metabolism and inflammatory signaling, immune microenvironment remodeling, and intestinal dysbiosis during this evolutionary process. It systematically summarizes key genes and potential therapeutic targets governing lipid metabolism in CAC and investigates the translational value of targeting lipid metabolic reprogramming for early intervention and combination therapies in CAC. By integrating current evidence, this article clarifies how lipid reprogramming orchestrates the inflammation-to-cancer shift, providing novel research insights and therapeutic strategies to improve clinical prognosis for CAC patients.

Pelvic inflammatory disease (PID) is a common infection among women of reproductive age, primarily caused by sexually transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae. Emerging evidence suggests that lipid metabolism may contribute to systemic inflammation and increased susceptibility to PID. This study aimed to explore the association between the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) and PID, and to assess the mediating role of inflammatory markers. This retrospective case-control study included 2,247 women diagnosed with or without PID based on surgical and clinical records at a single tertiary hospital. Least absolute shrinkage and selection operator (LASSO) regression was used to identify candidate predictors, followed by multivariate logistic regression. A PID prediction model was developed and evaluated using training and validation datasets (7:3 split). Mediation analysis assessed the role of inflammatory markers, particularly white blood cell (WBC) count. NHHR was significantly associated with PID (OR = 1.39, 95% CI = 1.16-1.66). Mediation analysis showed that WBC partially mediated the NHHR-PID relationship, accounting for 19.26% of the effect. The prediction model demonstrated strong discrimination, with AUCs of 0.825 (training) and 0.819 (validation). Higher NHHR levels are associated with an increased risk of PID, and systemic inflammation may partially mediate this relationship. NHHR may serve as a potential marker for PID risk stratification, though further external validation is warranted.

Objective biomarkers that reflect systemic inflammation in pediatric allergic rhinitis to support clinical diagnosis. We aimed to evaluate serum levels of endocan (a marker of endothelial activation) and eosinophil-derived neurotoxin (EDN; reflecting eosinophil degranulation) in children with AR and investigate their diagnostic performance and associations with disease severity and conventional inflammatory markers. In this prospective case-control study, 85 children with AR and 67 healthy controls were enrolled. Serum endocan and EDN were measured via sandwich ELISA. Primary outcomes included group comparisons of biomarker levels and their diagnostic accuracy determined by receiver operating characteristic (ROC) curve analysis. Serum endocan and EDN levels were significantly elevated in children with AR compared to controls (both p < 0.001). Both biomarkers demonstrated high diagnostic performance, with an area under the curve (AUC)&#xa0;of 0.931 for endocan and 0.929 for EDN, showing greater diagnostic accuracy than absolute eosinophil counts (AUC, 0.871). Endocan and EDN showed a strong intercorrelation (r = 0.88, p < 0.001) and significant positive correlations with total IgE and eosinophil counts. However, no significant associations were observed between these biomarkers and disease severity, symptom control scores, or allergen sensitization patterns. Serum endocan and EDN are significantly elevated in children with AR and demonstrate high diagnostic discrimination in this cohort. These findings suggest that endocan and EDN may serve as promising complementary biomarkers for the objective assessment of allergic inflammation in children, although further multicenter studies are needed to confirm their clinical utility. &#x2022; Allergic rhinitis (AR) is common in childhood and involves systemic inflammatory pathways; however, objective biomarkers to support diagnosis in pediatric practice remain limited. &#x2022; Endocan and eosinophil-derived neurotoxin (EDN) reflect endothelial activation and eosinophil degranulation, respectively, and have been studied in other atopic and inflammatory conditions. &#x2022; This study concurrently evaluates serum Endocan and EDN in children with AR in a prospective case-control design. &#x2022; Both biomarkers demonstrated high discriminatory performance (AUC&#x223c; 0.93 in this cohort) and showed greater diagnostic accuracy than absolute eosinophil counts&#xa0;. &#x2022; Endocan and EDN are largely independent of generalized systemic inflammatory indices (NLR, SII, SIRI), supporting specificity for the endothelial- eosinophilic axis in pediatric AR.

Development of a new ultrasound (US) synovitis score (SONography in Arthritis and Rheumatism (SONAR)-7) with evaluation of its diagnostic performance in a cohort of patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), in comparison with healthy controls (HC). We included 121 participants: 41 patients with PsA and 39 patients with axSpA, from six Swiss hospitals and 41 HC. All participants underwent a clinical examination of joints (68/66 tender joint count/swollen joint count (SJC)), followed by a detailed musculoskeletal US examination of 22 joints to assess for greyscale (GS) and power Doppler (PD) synovitis in adherence with the definitions established by the Outcome Measures in Rheumatology US working group. The 'SONAR-7' score incorporated GS and PD lesions across 14 joints, including four metacarpophalangeal joints, four distal interphalangeal joints of the hands, two metatarsophalangeal joints, knees and wrists. It demonstrated an area under the receiver operating characteristic curve of 0.831 (95% CI 0.76 to 0.90), with an excellent specificity (95.1%) and moderate sensitivity (44%), comparable to existing US scores. The inflammatory components of the SONAR-7 correlated significantly with clinical measures of inflammation and disease activity (correlation: 0.37 for SJC-28, 0.33 for Disease Activity in Psoriatic Arthritis and 0.48 for US enthesitis). New bone formation in the same joints was associated with the Health Assessment Questionnaire (p=0.035) and Bath Ankylosing Spondylitis Metrology Index (p=0.016). The SONAR-7 score represents a fast and effective US-based tool for the evaluation of inflammatory and structural joint involvement in patients with PsA and axSpA, with high specificity and meaningful associations with clinical and quality-of-life outcomes.

Micropulse transscleral cyclophotocoagulation (MP-TSCPC) has gained considerable acceptance as a preferred cyclodestructive intervention for refractory glaucoma, offering significantly enhanced safety profiles through precisely controlled pulse energy delivery while maintaining equivalent therapeutic outcomes compared with traditional modalities. To compare the efficacy and safety profiles of MP-TSCPC versus continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) in patients with refractory glaucoma. This prospective, randomized, single-blind study included 52 patients (52 eyes) with refractory glaucoma assigned to either MP-TSCPC or CW-TSCPC. Patients were followed for 18 months. Secondary outcomes included absolute IOP values, medication reduction, preservation of visual acuity, visual function parameters, quality of life, and complication rates. Success was defined as IOP between 6-21&#xa0;mm&#xa0;Hg without medications (complete success), with medications (qualified success), or either (cumulative success). Patients were followed for 18 months. At 18 months, 47 eyes completed follow-up (24 in MP-TSCPC and 23 in CW-TSCPC). The MP-TSCPC group (n=24) achieved a 34.43% IOP reduction from baseline, compared with 42.86% in the CW-TSCPC group (n=23), P=0.052. Complete success rates were 25.00% (6/24) for MP-TSCPC and 21.74% (5/23) for CW-TSCPC (P=0.999), while qualified success rates were 29.16% (7/24) and 39.13% (9/23), respectively (P=0.550). The cumulative success rates were 54.17% for MP-TSCPC and 60.87% for CW-TSCPC (P=0.706). The CW-TSCPC group experienced significantly higher rates of postoperative pain (56.52% vs. 20.83%, P=0.012) and prolonged inflammation (34.78% vs. 8.33%, P=0.039). Visual function parameters remained stable in both groups throughout the study period. Quality of life improved significantly in the MP-TSCPC group but not in the CW-TSCPC group, although between-group differences were not statistically significant. MP-TSCPC demonstrated comparable efficacy to CW-TSCPC in IOP reduction and success rates for refractory glaucoma management, while offering a significantly improved safety profile with less postoperative pain and inflammation. These findings suggest that MP-TSCPC may be considered as a preferred initial cyclodestructive option when balancing efficacy and safety, though larger studies are needed to confirm these findings.

Trauma is a leading cause of mortality worldwide. Accurate prognostic assessment in emergency departments and intensive care units is essential for effective triage and management. Consequently, various prognostic markers have been explored in trauma populations. The pan-immune-inflammation (PIV) is a biomarker derived from a complete blood count (CBC) and can be rapidly obtained in clinical settings. This study aimed to evaluate the role of PIV in predicting the prognosis of trauma patients. This study examined patients admitted to a tertiary-level intensive care unit due to trauma at a training and research hospital. Established prognostic parameters, including the Revised Trauma Score (RTS), Glasgow Coma Scale (GCS), and Acute Physi-ology and Chronic Health Evaluation II (APACHE II) scores, were evaluated. PIV values were calculated from laboratory data. Mortality, morbidity, and length of hospital stay were retrospectively analyzed. The predictive value of PIV for mortality was assessed using statistical methods. A total of 74 patients were included. The survivor group comprised seven females (11.5%) and 54 males (88.5%), while the non-survivor group included one female (7.7%) and 12 males (92.3%). PIV, RTS, GCS, and APACHE II scores were effective in predicting mortality (p<0.001). The cut-off value for PIV was 6367.5; patients with PIV values below this threshold had a higher risk of mortality compared to those with higher values. Rapid and reliable prognostication is essential in emergency settings. PIV demonstrates predictive performance comparable to established prognostic scoring systems. Early assessment of PIV in trauma patients may support more effective triage and treatment planning.

The therapeutic strategy for late-onset multiple sclerosis (LOMS) with a relapsing-remitting onset remains unclear, potentially leading to underexposure to disease-modifying therapies (DMTs) compared with adult-onset multiple sclerosis (AOMS). We investigated the differences in DMT use between LOMS and AOMS within the French MS registry at comparable levels of disease severity. This retrospective cohort study used data extracted in December 2024 from the French MS registry on patients with relapsing-remitting onset MS between 1997 and 2023. The primary outcome was the annual probability of receiving a DMT according to age at MS onset, adjusted for disease severity. Secondary outcomes included the annual probability of receiving a highly effective DMT (HEDMT), each DMT separately, having &#x2265;1 EDSS measurement, having &#x2265;1 brain MRI, and DMT initiations and discontinuations. We used a longitudinal logistic model with generalized estimating equations and an inverse-probability-of-censoring weighting. A total of 36,148 were included patients; 26,540 (73.4%) were female, mean age was 33.5 years (SD, 9.7), and 2,308 (6.4%) were aged &#x2265;50 at disease onset. Median follow-up was 10.8 years (interquartile range, 5.6-17.0). Patients with LOMS had a lower annual probability of receiving a DMT compared with patients with AOMS (73.7% vs 83.1%; odds ratio [OR], 0.57 [95% CI 0.52-0.62]). The difference was greater for HEDMT (24.6% vs 44.4%; OR, 0.41 [95% CI 0.36-0.46]). Patients with LOMS were more likely to receive teriflunomide and less likely to receive fumarates, S1PR modulators, natalizumab, or anti-CD20. Clinical and radiologic follow-up did not differ significantly between patients with LOMS and AOMS. The rate of DMT initiation was lower in patients with LOMS (0.13 vs 0.17 initiation per patient-year). Although the proportions of DMT discontinuation were similar (59.7% vs 60.4%, excluding pregnancy-related discontinuations), these discontinuations were more often attributed to a complete discontinuation strategy (27.9% vs 22.3%) and less often to an escalation strategy (9.2% vs 13.8%) in patients with LOMS. At comparable levels of disease severity, patients with LOMS were less likely to be treated with DMTs, particularly HEDMT, than patients with AOMS. This gap was driven both by fewer DMT initiations and more frequent complete discontinuations.

BackgroundClinicians encounter difficulties in differentiating between headache/facial pain of true sinogenic origin, and clinically similar pain related to primary headache disorders, such as migraine. The International Classification of Headache Disorders and International Classification of Orofacial Pain, together with clinical definitions of acute and chronic rhinosinusitis as refined by the European Position Paper on Rhinosinusitis and Nasal Polyps, have produced a unique opportunity to improve the current diagnostic criteria of headache/facial pain attributed to rhinosinusitis.MethodsAn international multidisciplinary panel reviewed clinical evidence regarding the overlap of primary headaches and rhinosinusitis in order to harmonize and clarify diagnostic frameworks.ResultsThe proposal integrates validated rhinologic definitions into headache and facial pain classifications. Key suggestions include the removal or adjustment of non-specific criteria (e.g., headache exacerbated by pressure applied over the paranasal sinuses) which also frequently occur in primary headache disorders. To enhance specificity, evidence-based negative predictors - such as the absence of nausea, osmophobia or photophobia and phonophobia - are introduced. Only for chronic rhinosinusitis, it has been proposed to include endoscopic or radiological evidence of inflammation, as necessary to confirm the diagnosis.ConclusionAligning ICHD-4 with contemporary rhinologic guidelines through the use of positive and negative predictors may help improve diagnostic accuracy, ensure appropriate therapy and increase the reliability of trial design.

Potassium superoxide (KO2), a superoxide anion donor, can be applied to induce reactive oxygen species (ROS) triggered pain and inflammation. trans-Chalcone (TC) is an atypical flavonoid because its molecular structure does not possess intrinsic antioxidant properties. This characteristic allows investigating the mechanisms of action of flavonoids excluding inherent chemical antioxidant effect. In the present study, we investigated the activity and mechanisms of TC in a model of inflammation and pain triggered by a superoxide anion donor, which to our knowledge have not been assessed yet. Overt pain-like behavior, mechanical hyperalgesia, edema, leukocyte recruitment, oxidative stress markers, cytokine dosage by enzyme-linked immunosorbent assay (ELISA), nuclear factor kappa B (NF-&#x3ba;B) phosphorylation by Western blotting, mRNA expression by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and neuronal activity by calcium levels were assessed. TC was administered orally 30 min before stimulation with KO2, and a dose of 30 mg/kg was selected based on previous study. TC inhibited abdominal contortion, mechanical hyperalgesia, paw edema, and myeloperoxidase activity (an indirect marker of macrophage/neutrophil recruitment). TC induced antioxidant activity (assessed by ferric reducing ability and free radical scavenging), while reducing superoxide anion production and lipid peroxidation, at least in part, by upregulating Nrf2 and downregulating Gp91phox and Cox-2 mRNA expression. TC inhibited KO2-induced NF-&#x3ba;&#x3b2; phosphorylation as well as interleukin (IL)-1&#x3b2;, tumor necrosis factor (TNF)-&#x3b1;, IL-6, and IL-33 production. Finally, TC reduced the activation of transient receptor potential vanilloid 1 (TRPV1+) and transient receptor potential ankyrin 1 (TRPA1+) nociceptive neurons in the dorsal root ganglia. These results demonstrate that the in vivo anti-inflammatory and analgesic activities of TC involve neuronal and non-neuronal mechanisms, and that non-antioxidant flavonoids are still biologically active.

Xuebijing (XBJ) injection is a traditional Chinese medicine (TCM) injection prepared using modern pharmaceutical techniques. Approved as a State Category II New Drug for sepsis, XBJ has demonstrated significant clinical efficacy in China. However, the bioactive components of XBJ and the mechanisms underlying its anti-sepsis effects remain to be fully elucidated. This study aimed to elucidate the regulatory network among herbs, compounds, genes, and signaling pathways. We conducted a network pharmacology analysis by integrating published RNA-sequencing data from the BioProject database and experimental evidence from 27 relevant studies identified in PubMed. And the anti-sepsis effects of XBJ and its main component, Hydroxysafflor Yellow A, were validated in a CLP-induced murine model. Our results demonstrate that XBJ modulates 21 target genes through at least 18 of its bioactive compounds (e.g. Quercetin, Kaempferol). The majority of these genes, including IL6, TNF, and HMGB1, were down-regulated after XBJ treatment. Using a cecal ligation and puncture (CLP)-induced murine sepsis model, we demonstrated that by 24&#xa0;hours post-operation, the survival rate in the XBJ-treated group was twice that of the PBS-treated group (66.7% vs. 33.3%). Finally, a comprehensive herb-compound-gene-pathway regulatory network was established to illustrate the potential mechanisms of action. In summary, this study reveals that XBJ may alleviate sepsis by modulating target genes via its compounds, primarily through anti-inflammatory and antioxidant pathways. This study provides a systematic elucidation of XBJ's anti-sepsis mechanism, and the research strategy established here offers a valuable framework for investigating the mechanisms of other complex traditional Chinese medicine formulae.

Acute kidney injury (AKI) after pancreaticoduodenectomy is common and early identification of such patients is critical. Inflammation contributes significantly to the onset of postoperative acute kidney injury. We aimed to construct and evaluate a predictive nomogram based on preoperative inflammatory indicators for postoperative AKI in patients undergoing pancreaticoduodenectomy. In the current retrospective cohort study, we included 844 adult patients who underwent pancreaticoduodenectomy between December 2016 and June 2020. All enrolled patients were randomly assigned to the training and validation cohorts in a 7:3 ratio. We utilized least absolute shrinkage and selection operator (LASSO) regression for feature selection and multivariable logistic regression analyses to identify key risk factors in the training cohort. These selected factors were subsequently used to construct a nomogram. The nomogram's performance was assessed using various metrics such as the receiver operating characteristic (ROC) curve, calibration curves, Hosmer-Lemeshow goodness of fit, and decision curve analysis (DCA). In this cohort, AKI was observed in 98 out of 844 patients, representing an incidence rate of 11.6%. LASSO regression and multivariable logistic analysis showed that monocyte-to-lymphocyte ratio (MLR), red blood cell distribution width (RDW), and alkaline phosphatase (ALP) were independent influencing factors of postoperative AKI. The nomogram, which integrated the three identified factors, demonstrated an area under the curve (AUC) of 0.799 in both the training and validation cohorts, indicating moderate discriminative ability. The Hosmer-Lemeshow goodness of fit test and the calibration curve demonstrate good agreement between predicted and observed values. The DCA indicated a positive net clinical benefit. We developed and validated a nomogram based on preoperative MLR that could help identify individuals at risk of AKI following pancreaticoduodenectomy. This model may help clinicians optimize perioperative management for these patients.

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health consequences experienced by spousal caregivers remain insufficiently characterized in the literature and inadequately addressed in clinical and public health practice. This structured narrative review synthesizes current evidence on the multidimensional impact of dementia caregiving on the physical, psychological, cognitive, social, and financial health of spousal caregivers. It further contextualizes these consequences within the trajectory of dementia progression, and identifies interventions, support systems, and policy considerations necessary to mitigate caregiver burden. Spousal caregivers experience disproportionate burden due to continuous, escalating responsibilities that often mirror the progressive deterioration of their partners. Emotional burdens, including uncertainty during pre-diagnostic stages, role strain, conflict, loss of intimacy, and anticipatory grief. Physically, spouses endure musculoskeletal strain, sleep disruption, poor nutrition, and heightened frailty risk. Psychologically, spousal caregivers exhibit elevated rates of depression, anxiety, loneliness, and stress-related disorders. Socially, caregivers experience substantial isolation, stigma, and erosion of social networks. Financial hardship, including early retirement, reduced employment, and uncompensated care hours, further exacerbate stress. Evidence suggests that chronic caregiving stress contributes to biological changes such as immune dysregulation, inflammation, acceleration, aging, and potential cognitive decline in caregivers themselves. Caregiver burden influences patient outcomes as evidenced by increased emergency department use, falls, and earlier institutionalization in persons with dementia whose caregiver is subjected to a high burden. Current care models rarely include routine, caregiver assessment or structured guidance following diagnosis, resulting in substantial unmet needs. Effective mitigation requires integrated, stage-sensitive interventions, including psychosocial support, caregiver education, respite services, culturally tailored programs, and digital health tools, alongside broader policy reforms to reduce financial and structural barriers.