Multidrug resistance (MDR) reduces chemotherapy efficacy and contributes to cancer relapse, making the development of low-toxicity MDR reversal agents essential. Xinjiang Euphorbia species have demonstrated potential as natural MDR reversers. This study aimed to identify MDR-reversal components from Xinjiang Euphorbia (Ep-XjC), investigate Rhamnetin's effect on the ABCB1 protein to clarify its MDR-reversal mechanism, provide new insights into Rhamnetin's anti-MDR properties, and support the development and application of anti-MDR constituents from Ep-XjC. Network pharmacology was used to screen compounds and predict targets, molecular docking and dynamics simulations to validate interactions, and in vitro assays to evaluate MDR reversal and ABCB1 modulation. Network pharmacology identified 388 potential target genes and 1732 MDR-related genes, with Rhamnetin (D37) showing the most promising results. Molecular docking and molecular dynamics simulations revealed stable interactions between D37 and ABCB1, the key protein responsible for MDR. Functional validation confirmed that D37 modulated ABCB1's functionality to reverse MDR without affecting its expression. The findings reveal Rhamnetin (D37) as a promising MDR reversal agent by modulating ABCB1 activity, highlighting Ep-XjCEuphorbia bioactive compounds as potential therapeutic strategies against cancer MDR. Further in vivo and clinical validation is warranted.

Vitamin D a fat-soluble steroid hormone signals through Vitamin D Receptors (VDRs) located throughout the ovaries, uterus, placenta, hypothalamus, and pituitary gland, influencing immune regulation and female reproductive physiology. This review of studies from 2013-2025 found consistent associations between low vitamin D status and various disorders in women of childbearing age. In Premenstrual Syndrome (PMS), deficiency correlates with higher symptom severity, and evidence shows that supplementation significantly reduces total PMS scores, particularly improving mood-related domains. For uterine pathologies such as fibroids, endometriosis, and adenomyosis, low vitamin D status is linked to increased risk and severity. Repletion trials suggest antifibrotic and analgesic benefits, although larger, more rigorously designed studies are still needed for definitive clinical guidelines. In Polycystic Ovary Syndrome (PCOS), low vitamin D links to adverse metabolic and hormonal profiles. Multiple randomized controlled trials (RCTs) confirm that correcting deficiency improves insulin resistance, lowers total testosterone and free-androgen index, raises sex-hormone-binding globulin (SHBG), and helps regularize menstrual cycles. Targeted supplementation is recommended, especially for insulin-resistant or obese phenotypes. During pregnancy, maternal deficiency is associated with adverse outcomes including pre-eclampsia, gestational diabetes, and pre-term birth risk. However, intervention trials have yielded inconsistent preventive results, often complicated because rising Vitamin D-Binding Protein (VDBP) may mask true vitamin D status. In Assisted Reproduction like In Vitro Fertilization (IVF), correcting deficiency early during pre-conception or early folliculogenesis appears beneficial. This early dosing enhances oocyte quality, promotes granulosa cell proliferation, and modulates local transcriptomes toward anti-inflammatory pathways. In contrast, single high-dose boluses administered shortly before embryo transfer show limited impact on outcomes. The overall evidence is limited by heterogeneous study designs, variable dosing, and reliance on total serum levels rather than bioavailable vitamin D. Future research should prioritize large, multicenter RCTs utilizing standardized daily/weekly dosing, stratifying by genetic and phenotypic factors, and measuring bioavailable vitamin D to establish reliable effects on patient-centered outcomes.

This study investigated the role of UCHL5 in thyroid carcinoma (THCA) progression, focusing on its tumor-suppressive mechanisms and regulation of ferroptosis.

We performed multi-omics analysis of TCGA and GEO datasets and validated the findings using clinical samples. The CRISPR/Cas9-mediated knockout and stable overexpression in THCA cell lines were constructed, followed by comprehensive functional assays including co-immunoprecipitation (Co-IP), ubiquitination analysis, xenograft tumor models, and ferroptosis sensitivity tests using erastin/ferrostatin-1 with BODIPY C11 lipid ROS measurement. Weighted gene co-expression network analysis (WGCNA) was performed to identify hub genes and to analyze associated pathways.

Clinical data revealed significant downregulation of UCHL5 in advanced thyroid cancers, particularly in lymph node metastases. UCHL5 knockout markedly accelerated cell proliferation and xenograft tumor growth, while its overexpression suppressed both. Mechanistically, we identified a direct interaction between UCHL5 and ZRANB1 through co-IP, with UCHL5 extending the protein half-life of ZRANB1 by over 2-fold. In ferroptosis regulation, erastin treatment (10 μM) revealed that UCHL5 overexpression enhanced sensitivity, while UCHL5 knockout conferred significant protection, accompanied by altered GSH levels, Fe²⁺ accumulation, and lipid ROS production. Western blot analysis revealed that UCHL5 upregulated ZRANB1 and downregulated SLC7A11/GPX4 expression.

This study demonstrates that UCHL5 acts as a critical tumor suppressor in thyroid cancer by stabilizing ZRANB1 through deubiquitination and regulating ferroptosis via the SLC7A11-GPX4 axis.

Objective:To investigate the expression of HPV 6/11 in NIP tissues and evaluate the adjuvant therapeutic effect of interferon-α gel on HPV-positive NIP patients. Methods:Forty-two newly diagnosed Nasal Inverted Papilloma（NIP） patients were included, and the expression of HPV6/11 in tissues was detected using fluorescence in situ hybridization with specific probes. Twenty-two HPV-positive patients were randomly divided into an interferon treatment group（n=11） and a control group（n=11）. Both groups underwent endoscopic tumor resection, with the treatment group receiving local application of interferon-α gel during and after surgery. Postoperative recovery was assessed using the DIP endoscopic scoring system at 3, 6, and 12 months. Results:The positive expression rate of HPV6/11 in NIP tissues was 52.38%（22/42）, which was significantly higher than that in the nasal polyp control group（8.33%, 1/12）（P<0.05）. Among HPV-positive NIP patients, there were no statistically significant differences were observed in DIP scores between the interferon treatment group and the control group at 3, 6, and 12 months postoperatively（P>0.05）. Conclusion:HPV6/11 shows high expression in NIP tissues, but the use of interferon-α gel did not improve postoperative recovery in HPV-positive patients.

Cardiovascular-kidney-metabolic (CKM) syndrome is a recently proposed framework emphasizing the interconnected nature of cardiovascular, kidney, and metabolic disorders. These conditions share risk factors with cancer, but the relationship between CKM stage and cancer risk remains unclear. We aimed to investigate a longitudinal association in a large-scale, nationwide population.

We conducted a retrospective cohort study using the DeSC administrative claims database in Japan, including individuals who had available health checkup data and insurance claims between April 2014 and August 2023. After excluding those with prior cancer or missing covariates, 1 390 901 participants were analyzed. Baseline CKM stage (0-4) was defined according to the 2023 American Heart Association statement, incorporating cardiometabolic risk, chronic kidney disease, and atherosclerotic cardiovascular disease. The primary outcome was incident cancer (International Classification of Diseases, Tenth Revision codes C00-C97). Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusting for demographic, clinical, and lifestyle factors. Subgroup and sensitivity analyses were also performed.

Over a median follow-up of 3.4 years, higher baseline CKM stages were associated with increased cancer risk. Adjusted hazard ratios (95% CIs) for cancer were 1.03 (0.99-1.08), 1.02 (0.99-1.05), 1.25 (1.21-1.29), and 1.30 (1.25-1.35) for CKM Stages 1-4, respectively, compared with Stage 0. The stage-specific association was consistent across cancer types and in analyses stratified by age and sex, with similar patterns observed across subgroups. Sensitivity analyses using alternative CKM definitions supported the robustness of the findings.

Advancing baseline CKM stage, particularly Stages 3 and 4, was associated with increased cancer risk. These findings extend the clinical relevance of the CKM framework beyond cardiovascular and kidney outcomes, underscoring the need for integrated risk assessment and prevention in multimorbid individuals.

Background. Membranous nephropathy (MN) is generally primary, but it can also occur as a secondary form in association with infections, neoplasms or autoimmune diseases. Systemic Sclerosis (SSc), especially in its sine scleroderma forms or in its early stages, rarely manifests itself as MN. Case report. A 60-year-old woman with onset of nephrotic syndrome and histological picture of MN, in the absence of systemic manifestations. The patient subsequently developed episodes of acute renal failure, recurrent proteinuria and clinical-serological signs suggestive of autoimmune connective tissue disease, including increasing ANA titre with anticentromere pattern and onset of Raynaud's phenomenon. The second renal biopsy showed an evolving picture with extensive interstitial fibrosis and severe arteriosclerosis, consistent with a secondary form of MN. The patient was treated with the Ponticelli regimen and subsequently with rituximab, achieving significant clinical remission. In light of the capillaroscopy and autoantibody profile, a diagnosis of very early systemic SSc (sine scleroderma) was made. Discussion. This case highlights how MN can represent an early and atypical manifestation of SSc sine scleroderma, preceding systemic manifestations by years. The negative anti-PLA2R test, the presence of antinuclear autoantibodies and rapid histological progression pointed towards a secondary autoimmune aetiology. Repeated renal biopsy and immunological monitoring proved to be key tools for diagnosis and therapeutic management. Conclusion. MN secondary to SSc sine scleroderma is a rare but important condition that requires attention and a multidisciplinary approach. Early classification as a secondary form allows for targeted therapy and potentially prevents progression to end-stage renal failure.

This study aimed to apply ultra-broadband micromechanical ultrasound (UMUS) for correction of myelosuppression caused by the cytotoxic effects of cyclophosphamide without limiting its antitumor efficacy.

The study included animals bearing transplanted Ehrlich carcinoma. Cyclophosphamide (CP) was administered once daily for three consecutive days starting on day 8 of tumor growth at a cumulative dose of 330 mg/kg per mouse. After completion of CP administration, a subset of animals was exposed to UMUS irradiation once daily for five days. Control groups included mice without tumors and tumor-bearing mice not exposed to CP or UMUS. Tumor growth kinetics were analyzed, and quantitative parameters of peripheral blood, bone marrow, and spleen were determined.

The obtained data indicate that UMUS exposure does not reduce the antitumor efficacy of CP but is associated with enhanced recovery of the hematopoietic system and exerts a positive effect on bone marrow regeneration. This is confirmed by a statistically significant increase in the number of cells in specific bone marrow hematopoietic pools, including myelokaryocytes, blast cells, erythroid, lymphoid, and megakaryocytic cells.

UMUS exposure was associated with accelerated recovery of multiple hematopoietic lineages in the bone marrow following cyclophosphamide-induced injury, without compromising antitumor efficacy.

Ewing Sarcoma of the pelvis has poorer outcomes than other anatomical sites, with complex anatomy often precluding resection with wide margins. The role of postoperative radiotherapy (RT) in improving outcomes remains undefined. A systematic review using Medline, Embase and Cochrane databases (1972-April 2024) evaluated postoperative RT's impact on local recurrence, event-free survival and overall survival. Twenty-nine retrospective studies (21 to 296 patients) met inclusion criteria, with 28 rated good quality. Seven of 14 studies showed improved local control with postoperative RT. Ten studies reported consistent but non-significant trends favoring postoperative RT for event-free survival. Nineteen studies reported mixed overall survival findings; the Euro-EWING 99 trial showed significantly improved 5-year survival (72% vs. 47%, p = 0.024), while others showed conflicting results. Postoperative RT should be considered for high-risk features including poor response to induction chemotherapy, large tumour volume (> 200 mL) and positive margins. Clinical trial participation should be encouraged. Trial Registration: PROSPERO registration number: CRD42021291665.

Nodular basal cell carcinoma (nBCC) of the face can be challenging to diagnose in its early stages. We report our observation of a simple and rapid clinical maneuver that enhances the visualization of arborizing vessels, erosions, and bleeding, thereby facilitating the identification of nBCC. This preliminary observation suggests that the technique may reduce unnecessary biopsies, preserve cosmetic outcomes, and support timelier patient management.

Craniopharyngiomas are benign sellar and parasellar tumors and clinically challenging to treat because of their proximity to the critical neurovascular and hypothalamic structures. Recently, distinct driver mutations, including CTNNB1 in adamantinomatous craniopharyngiomas and BRAF V600E in papillary craniopharyngiomas, have led to a paradigm shift in treatment strategies. Endoscopic endonasal transsphenoidal surgery, supported by advances in surgical instruments and techniques, has expanded the indications for this minimally invasive surgical strategy, which has become an important approach in contemporary surgical management. Radiotherapy remains an effective adjuvant option for residual or recurrent tumors and contributes to durable local tumor control if combined with function-preserving surgical strategies. Molecular targeted therapy combining BRAF and MEK inhibitors results in marked tumor shrinkage in papillary craniopharyngiomas harboring the BRAF V600E mutation. These agents have emerged as promising therapeutic options, potentially as neoadjuvant therapies for enhancing surgical safety or achieving non-surgical tumor control in selected cases. Future management of craniopharyngiomas requires an individualized, multimodal approach that integrates the molecular subtype, patient age, functional status, and long-term quality of life to choose a treatment course that balances durable tumor control with optimal functional outcomes.