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Background: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC.

Methods: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening.

Discussion: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies.

Conclusion: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Background: Nemolizumab, an anti-IL-31 receptor A antibody, is licensed for atopic dermatitis and prurigo nodularis; its role in other chronic pruritus (CP) syndromes is uncertain.

Objective: To synthesize efficacy, safety and strength of evidence for nemolizumab in CP beyond these indications. Methods: We conducted a PROSPERO-registered systematic review (CRD420251207054) of databases and trial registries to November 2025 for nemolizumab studies in CP outside AD/PN. Eligible reports were extracted and patients grouped as systemic, neurologic/neurogenic, dermatologic (non-AD) or primary CP/CP of unknown origin.

Results: Seventeen reports (one randomized trial, two cohorts, 14 case series/reports) describing 114 patients were included. In chronic kidney disease-associated pruritus, a phase II hemodialysis trial showed modest, statistically uncertain benefit versus placebo, contrasting with rapid, near-complete relief in dialysis and cholestatic case reports. Uncontrolled data in neuropathic itch/pain syndromes, non-AD inflammatory and papular dermatoses (notably amyloidosis and perforating disorders) and long-standing primary CP/CPUO described complete itch clearance. Across indications, nemolizumab was well tolerated, but certainty was low for CKD-aP and very low for other groups.

Conclusions: Nemolizumab shows plausible antipruritic activity across CP phenotypes, yet the evidence base remains fragile; these signals justify cautious experimental use and prioritize etiology-specific IL-31 receptor blockade trials beyond AD/PN.

Objective: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA).

Methods: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0.

Results: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear.

Conclusion: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Background: Seasonal affective disorder (SAD) is a major depressive disorder recurring in fall and winter due to daytime light deficiency. To investigate underlying mechanisms of SAD, we previously developed a diurnal model using Nile grass rats (Arvicanthis niloticus), in which a winter-like dim daylight condition (dimLD) increased depression-like behaviors and neuroinflammation, while attenuating central orexinergic activity compared to grass rats housed in a summer-like bright daylight condition (brLD).

Materials and methods: The present study tested the hypothesis that the behavioral and neuroinflammatory responses induced by the winter-like dimLD condition are due to attenuated central orexinergic output. Male and female grass rats housed in dimLD or brLD received intracerebroventricular orexin A (OXA) or vehicle (aCSF) 6 h every morning for one week while sleep/wakefulness were continuously monitored. A saccharin-solution preference test was performed on the last infusion day to assess anhedonia, followed by brain collection for analyzing neuroinflammatory markers in the medial prefrontal cortex, dorsal hippocampus, and basolateral amygdala.

Results: OXA treatment promoted daytime wakefulness in females, improved nighttime sleep quality in males, and reduced anhedonia in both sexes of dimLD animals to levels comparable to brLD-aCSF controls. Additionally, treating dimLD animals with OXA increased expression of anti-inflammatory cytokines IL-4 and IL-10, and reduced pro-inflammatory markers including IL-6, CD11b, and the number and inflammatory morphology of microgliadepending on sex and brain site.

Conclusions: These findings support the hypothesis that the orexinergic system mediates the effects of ambient light on sleep and affect, and may be a potential therapeutic target in SAD.

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: Sarcopenic obesity (SO) is a multifactorial condition characterized by the coexistence of excess adiposity and reduced skeletal muscle mass and function. Its development reflects a complex interaction of metabolic, inflammatory, and endocrine mechanisms that disrupt the balance between anabolic and catabolic processes.

Main findings: Endocrine dysfunction is a major driver of the altered adipose-muscle crosstalk characteristic of SO. Hormonal imbalance amplifies mitochondrial dysfunction, oxidative stress, and chronic inflammation, leading to reduced muscle quality and increased visceral and intramuscular fat. Age-related hormonal decline, including reductions in testosterone and estrogens, growth hormone (GH), insulin-like growth factor 1, and thyroid hormones, together with increased catabolic activity of glucocorticoids and the renin-angiotensin-aldosterone system, as well as altered sympathoadrenal signaling, promotes insulin resistance, muscle catabolism, and fat accumulation. Beyond aging, endocrine diseases such as hypogonadism, GH deficiency, hypothyroidism, Cushing syndrome, hyperaldosteronism, and diabetes replicate many features of SO and serve as valuable models for investigating its underlying mechanisms.

Future directions: Emerging anabolic or anti-catabolic agents, such as Selective Androgen Receptor Modulators (SARMs), myostatin inhibitors, and ghrelin analogues, show promise but require further validation. Future research should explore endocrine disorders as experimental models of SO, focusing on the shared molecular and hormonal mechanisms that link fat accumulation and muscle loss. Finally, studying endocrine pathways in an integrated manner, rather than focusing on obesity and sarcopenia separately, may identify new hormonal targets for precision therapies aimed at restoring anabolic-catabolic balance and improving metabolic and functional outcomes in individuals with SO.

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.