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Background: Some intracranial aneurysms (IAs) still develop in-stent stenosis (ISS) even after successful pipeline embolization device (PED) implantation. ISS increases the risk of retreatment and ischemic complications, thereby affecting the long-term prognosis of IA patients. This study aims to identify predictors for ISS after PED treatment of IAs, and develop a nomogram for assessing individual risk.

Materials and methods: This analysis included unruptured IA patients treated with PEDs between April 2016 and October 2023 at three institutions. The patients were grouped into the training cohort and validation cohort according to the admission institution. Predictors were identified via least absolute shrinkage and selection operator analysis and multivariable regression analysis. A nomogram was then developed to predict ISS after PED implantation in the training cohort. The area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate the predictive accuracy and clinical value of the nomograms.

Results: A total of 1335 IA patients were included in this study (1049 in the training cohort and 286 in the validation cohort). A total of 139 (13.3%) and 41 (14.3%) patients developed ISS in the training cohort and validation cohort, respectively. A nomogram with five predictors (difference between the proximal and distal parent artery diameters, distal stent-to-vessel diameter ratio, overlapping devices, balloon angioplasty, and dissecting aneurysms) was developed via multivariate logistic regression analysis. AUCs of the nomogram in the training cohort and validation cohort were 0.836 (95%CI, 0.801-0.870) and 0.829 (95%CI, 0.770-0.888), respectively. Calibration curve and DCA analysis confirmed the utility and clinical applicability of this nomogram.

Conclusion: This nomogram showed high accuracy and clinical utility in predicting ISS after PED treatment, indicating that the nomogram can guide the identification of high-risk patients and the development of improved treatment strategies.

Objectives: To examine whether the JAK inhibitor tofacitinib alleviates secretory dysfunction and modulates Th17/Treg balance in a Sjögren's disease (SjD) murine model.

Methods: Integrated analysis of SjD transcriptome sequencing (GSE159574, GSE247662) identified key signalling pathways, potential therapeutic agents, and immune cell infiltration. NOD/ShiLtj mice were administered with or without tofacitinib. Secretory function and inflammation were assessed via fluorescein ocular surface staining, tear flow rate, histopathology (HE, Masson, Sirius Red), saliva flow rate, immunohistochemistry, immunofluorescence, flow cytometry, and cytokine measurement. Pearson's linear regression evaluated the correlation between Th17/Treg balance and secretory function.

Results: Bioinformatics analysis showed the JAK-STAT pathway and CD4+ T cells contribute to SjD pathogenesis. Tofacitinib reduced corneal fluorescein staining, increased tear break-up time and secretion, diminished salivary gland lymphocytic inflammation, improved saliva flow rate, and altered phospho-JAK3-STAT1 expression. It also reduced Th17 cell proportion, increased Treg cell proportion in salivary glands and spleens, decreased IL-17, and increased IL-10 and TGF-β in blood. A strong negative correlation existed between secretory function and Th17/Treg balance.

Conclusions: Tofacitinib potently attenuated secretory dysfunction and inflammation in SjD mice, possibly by modulating Th17/Treg balance, suggesting it may be a therapeutic agent for SjD.

Background: Neuropathic pain (NP), resulting from damage or disease affecting the somatosensory nervous system, severely impairs patients' quality of life and constitutes a substantial global disease burden. Recent evidence highlights the critical involvement of mechanosensitive ion channels in peripheral nociception.

Discussion: This review systematically examines the roles of key mechanosensitive channels in NP pathophysiology. TRPV4 mediates mechanical allodynia via ion flux modulation and neuroinflammation; TRPC6 enhances neuronal excitability through calcium dynamics and MAPK/mTOR signaling; TRPA1 regulates pain through neuronal and Schwann cell mechanisms involving the NOX1-oxidative stress-CXCL1 axis and myelin disruption; TREK channels attenuate pain by stabilizing resting membrane potential; TMEM family members modulate neuroimmune signaling; and Piezo2 critically contributes to mechanical and inflammatory hypersensitivity. These mechanisms reveal significant translational potential for analgesic development.

Conclusions: Targeted modulation of mechanosensitive ion channels represents a promising strategy for developing effective, non-addictive analgesics. This review establishes a theoretical foundation for understanding NP pathophysiology and identifies actionable therapeutic targets with substantial clinical relevance.

Background: Patients with both acute myocardial infarction (AMI) and chronic kidney disease (CKD) face a markedly poor prognosis, a key driver of which is insulin resistance (IR). This study aims to systematically evaluate and compare the predictive performance of four commonly used IR indices for major adverse cardiovascular events (MACE), and to assess their incremental value over the GRACE score in this patient group.

Methods: This retrospective cohort study analyzed 1,803 patients with AMI and CKD. Multivariable Cox regression determined associations between IR indices and MACE. Predictive performance was evaluated using C-statistics, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI).

Results: During a median follow-up of 28.2 months, 462 MACE occurred. Patients with MACE were older, had higher female proportion, elevated GRACE score, and increased diabetes prevalence (all p < 0.05). the triglyceride-glucose (TyG) index and the atherogenic index of plasma (AIP) demonstrated linear associations with MACE risk, whereas TyG-body mass index (TyG-BMI) and metabolic score for insulin resistance (METS-IR) exhibited U-shaped nonlinear relationships (p < 0.001). The Area Under the Curve (AUCs) for MACE prediction were: TyG index 0.62, AIP 0.57, TyG-BMI 0.58, and METS-IR 0.56. Incorporating IR indices significantly enhanced the GRACE score's predictive capacity, with TyG index providing the greatest incremental improvement (cNRI = 0.137, IDI = 0.03).

Conclusion: IR indices predict outcomes in patients with AMI and CKD and enhance GRACE score prediction, with TyG index demonstrating superior performance.

Background: Adhesive capsulitis (AC) is a chronic inflammatory condition with limited range of motion (ROM) in the glenohumeral joint. The main goals in managing AC are pain reduction and returning joint function. Intra-articular hyaluronic acid (HA) has been considered a safe modality in AC. This study compared the effectiveness of intra-articular injection of low molecular weight (LMW) with high molecular weight (HMW) HA in patients with AC.

Methods: Fifty-six patients with AC were randomized in this triple-blinded clinical trial. All underwent standard physical therapy. The outcomes were visual analog scale (VAS), Oxford shoulder score (OSS), active ROM, and patient satisfaction at 4, 12, and 24 weeks.

Results: No significant differences were detected in between-group variables at baseline. Both groups showed marked improvement in VAS, OSS, and ROM over time. At four weeks LMW-HA group had lower pain (P = 0.049). Conversely, the trend of VAS at 12-week and 24-week endpoints favors HMW-HA (Baseline to endpoint: -5.48 ± 1.68 and -3.91 ± 1.31 reduction in VAS as the primary outcome, P < 0.001). Satisfaction had significantly improved in both groups.

Conclusion: HMW-HA was associated with greater pain reduction and functional improvement compared with LMW-HA.

Trial registration: The trial protocol was registered at the Iranian Registry of Clinical Trials (IRCT), a WHO Primary Register setup (registration No: IRCT20170608034390N4; First registration date: 01/01/2020).

Aim: Given the chronic nature of acne, two 6-month studies were conducted to evaluate the long-term efficacy and tolerability of clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB)-the only approved triple-combination acne topical-and its effects on scarring/dyspigmentation in participants with moderate to severe acne.

Materials and methods: Data were pooled from 2 identical, open-label, single-center studies conducted in participants (N = 50) aged ≥12 years with Investigator's Global Assessment (IGA) score of 3/4. Endpoints included change from baseline in IGA score, inflammatory/noninflammatory lesions, skin appearance (dryness, postinflammatory hyperpigmentation [PIH], postinflammatory erythema [PIE]), and scarring. Adverse events and tolerability (itching, burning, redness, swelling) were assessed.

Results: At week 24, 67% of participants achieved treatment success, and significant reductions from baseline in inflammatory (88%) and noninflammatory (68%) lesions were observed (p < 0.001, both). Significant reductions in scarring (33%), investigator- and participant-assessed PIH (71%; 78%, respectively), and PIE (77%; 77%, respectively) were demonstrated (p < 0.001, all). Most participants (>70%) reported no tolerability issues throughout the studies. Seven adverse events occurred; 4 were related to CAB, and 3 led to study discontinuation (BPO allergy [n = 2], irritant contact dermatitis to BPO [n = 1]).

Conclusions: These findings suggest that CAB is an appropriate and effective topical option for the long-term treatment of acne vulgaris.

Objectives: Vitiligo is an autoimmune skin disorder characterized by melanocyte destruction and frequently associated with autoantibodies such as antinuclear antibodies (ANA). However, the clinical relevance of ANA positivity in relation to phototherapy response remains unclear. This study aimed to evaluate whether ANA positivity influences the efficacy and safety of 308-nm excimer light therapy in patients with vitiligo.

Methods: In this cohort study, 86 patients with vitiligo received 308-nm excimer light therapy combined with topical agents, with oral mini-pulse prednisone added for active disease when necessary. Patients were stratified by ANA status, and therapeutic response was evaluated using the Vitiligo Area Scoring Index and standardized photographs over 6 months.

Results: Of the 23 ANA-positive patients (26.7%), 19 (82.6%) had a titer of 1:100 and 4 (17.4%) had a titer of 1:320, with women comprising 73.9% of this group. ANA-positive lesions on the face and neck more frequently achieved moderate repigmentation (50-74%) but were less likely to reach excellent repigmentation (≥75%) compared with ANA-negative lesions. No significant differences were observed in cumulative treatment doses, adverse events, or the occurrence of new autoimmune conditions.

Conclusions: In conclusion, this single-center cohort study suggests that ANA positivity does not significantly affect the efficacy or safety of 308-nm excimer light therapy in vitiligo, indicating that the impact of low-titer ANA may be limited.