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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.

Background: Chimeric antigen receptor (CAR) -T cell therapy has emerged as a promising approach for treating severe autoimmune diseases (AIDs), offering distinct advantages over conventional immunosuppressive therapies. This review examines recent advancements in both autologous and allogeneic CAR-T platforms for AIDs.

Methods: We analyzed preclinical and clinical evidence regarding CAR-T therapies. These therapies target signaling molecules across various cells in the myeloid and lymphoid lineages, addressing autoimmune pathologies across dermatological, neurological, gastrointestinal, and hematological systems.

Results: Diversified CAR-T technological innovations have been developed. CAR-T therapy achieves remarkable efficacy in various AID by precisely eliminating pathogenic cells and facilitating a systemic immune reset, thereby maintaining a favorable balance between therapeutic benefit and safety.

Conclusion: CAR-T cell therapy represents a revolutionary therapeutic strategy for the management of refractory AIDs. Addressing current challenges will further promote its clinical translation and expand its application in the treatment of AIDs.

Objective: To investigate the clinical characteristics and impact of SMARCA4 mutations in patients with non-small cell lung cancer (NSCLC).

Methods: A total of 2,821 patients with NSCLC who underwent next-generation sequencing were retrospectively included. The frequency and types of SMARCA4 mutations and co-mutations were determined, and the clinical outcomes were assessed.

Results: SMARCA4 mutations were identified in 100 samples (3.54%), and 36% were missense mutations. The most frequent co-mutations were TP53 (67%) and EGFR (31%); 13% of SMARCA4 mutations occurred in samples carried EGFR and TP53 mutations. Notably, 63% SMARCA4 mutations did not present druggable driver mutations. SMARCA4 mutations were most prevalent in males and smokers. Patients with SMARCA4 mutant lung adenocarcinoma (LUAD) and EGFR mutations who received EGFR-tyrosine kinase inhibitors (EGFR-TKI) as first-line therapy had a lower objective response rate (ORR, 52.94%). In SMARCA4 mutation and EGFR wild-type (wt) NSCLC cohort who received first-line chemotherapy, age (hazard ratio [HR], 3.090; p = 0.026) and performance score (HR, 5.848; p = 0.045) were identified as independent predictors of progression-free survival (PFS). Conversely, brain metastasis was an independent predictor of superior overall survival (HR, 0.188; p = 0.011). The patients with EGFR wt and SMARCA4 mutant Stage IV LUAD who received chemotherapy plus anti-angiogenic therapy significantly improved median PFS compared to chemotherapy alone (p = 0.04).

Conclusions: SMARCA4 mutations were predominantly males and smokers in NSCLC. SMARCA4 mutations conferred a poorer response for EGFR-mutant LUAD subgroups who received EGFR-TKIs. Additionally, chemotherapy plus anti-angiogenesis as first-line therapy may be more effective for Stage IV-SMARCA4 mutant LUAD with EGFR wt.

Background: Post-intensive care syndrome (PICS) is a post-discharge complication from the intensive care unit (ICU) that manifests as a range of physical, cognitive, and psychological impairments for patients. Given the growing number of ICU survivors and the vital role of this syndrome in identifying individuals at risk of deterioration after ICU discharge, we conducted a systematic review and meta-analysis to assess the prevalence and incidence of PICS.

Method: Between January 1, 2010, and October 5, 2024, a thorough search was conducted across the Web of Science, PubMed, Scopus, Embase, Cochrane Library, and CINAHL databases. Cross-sectional and cohort studies were included. The prevalence and incidence of PICS, as determined by any assessment method, were the primary study outcomes. PICS was defined according to the criteria used in each primary study. A meta-analysis was performed using a random-effects model. Meta-regression analysis was employed to investigate the impact of distinct follow-up durations on the reported prevalence and incidence. The JBI critical appraisal tool for prevalence studies was used to assess the risk of bias in the included studies.

Results: This systematic review and meta-analysis synthesised data from 34 studies involving 6230 participants. The pooled prevalence and incidence of PICS were 60.3% (95% CI: 48.5-72.1) and 52.4% (95% CI: 47.6-57.2), respectively. The I² statistic for heterogeneity in the included prevalence and incidence studies was 98.67% and 81.23%, respectively. Subgroup analyses by country, cutoff definition, and underlying participant disease revealed a substantial reduction in heterogeneity. Only the use of a cutoff substantially reduced heterogeneity in reported incidence across studies.

Conclusion: This systematic review and meta-analysis demonstrate a notable prevalence and incidence of PICS among ICU survivors. These findings highlight the need for early detection of at-risk individuals and the development of evidence-based approaches to monitor and address impairments related to PICS.

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.