Dysregulated lipid metabolism and chemoresistance are key drivers of breast cancer progression. Lectin, mannose-binding 2 (LMAN2) is frequently overexpressed in human breast tumors and functions as an oncogenic driver. However, whether LMAN2 contributes to chemoresistance remains unknown. We integrated multi-omics data from 1,085 primary tumors and matched normal tissues (from GEPIA and UALCAN) with functional studies in breast cancer cell lines and a doxorubicin (ADM)-treated nude mouse xenograft model. LMAN2 expression was modulated via siRNA/shRNA-mediated silencing or lentivirus-driven overexpression. Cellular phenotypes-including proliferation, migration, apoptosis, and response to ADM were systematically assessed. RNA-sequencing, untargeted lipidomics, and rescue experiments identified stearoyl-CoA desaturase (SCD) as a critical downstream effector. IC50 shifts and epistasis analysis further validated the role of the LMAN2/SCD axis in chemoresistance. LMAN2 mRNA was elevated across all molecular subtypes (luminal > HER2 > triple-negative) and predicted poorer overall survival (P = 5 × 10−4) and progression-free survival (P = 0.018). Silencing LMAN2 reduced clonogenicity by 45

Background:The optimal extent of surgery for patients with unilateral multifocal papillary thyroid carcinoma (PTC; ⩽4 cm) and limited lymph node metastasis remains uncertain. Objectives:To compare recurrence risk between lobectomy and total thyroidectomy in this population. Design:Retrospective cohort study with inverse probability weighting regression adjustment (IPWRA) and non-inferiority analysis. Methods:This study included unilateral multifocal PTC (⩽4 cm) patients without bulky nodes (all metastatic <3 cm) treated from 2008 to 2024. IPWRA estimated the average treatment effect (ATE) of lobectomy versus total thyroidectomy on recurrence. A non-inferiority analysis with a prespecified margin of 3% was performed. Sensitivity analyses included traditional multivariable logistic regression, 1:1 propensity score matching, weighted logistic regression, and a 5-year landmark analysis. Recurrence-free survival was analyzed using Kaplan-Meier methods and multivariable Cox regression. Results:A total of 1373 patients were included (524 lobectomy, 849 total thyroidectomy). After IPWRA, all covariates achieved excellent balance. Over 52.4 months median follow-up, 36 recurrence events occurred (2.6%). The ATE of lobectomy versus total thyroidectomy was 1.19% (95% confidence interval (CI): -1.44% to 3.81%; p = 0.375), indicating no statistically significant difference in recurrence risk between the two procedures. The upper bound of the 90% CI (3.39%) marginally exceeded the prespecified non-inferiority margin of 3%. The 5-year landmark analysis showed a near-zero difference (ATE 0.01%, p = 0.994), and three of four sensitivity analyses yielded nonsignificant results. Subgroup analyses were directionally consistent but underpowered. The multivariable Cox regression was underpowered (minimum detectable hazard ratio (HR): 2.61) and yielded an inconclusive result (HR: 2.04, 95% CI: 0.91-4.62, p = 0.085). Conclusion:In patients with unilateral multifocal PTC (⩽4 cm) without bulky nodal metastases, lobectomy showed no significant difference in recurrence risk compared with total thyroidectomy, supporting that lobectomy may be a safe alternative in this intermediate-risk population.

Germline BRCA1/2 pathogenic or likely pathogenic variants (PVs) are well-established genetic risk factors for breast cancer. However, most previous studies focused on Western populations, leaving a gap in the characterization of Asian cohorts. Therefore, we conducted a retrospective analysis across three hospitals in Northwest China, aiming to elucidate the clinical implications of BRCA PVs in this understudied population. This multi-center, retrospective cohort analysis investigated the influence of BRCA PV status on the response to neoadjuvant chemotherapy (NAC) and prognosis. We enrolled 1009 stage I-III breast cancer patients who underwent germline BRCA1/2 testing and received at least four cycles of a standard NAC regimen between January 1, 2017, and August 31, 2025. The primary endpoint was pathological complete response (pCR), and the secondary endpoint was event-free survival (EFS). Of the 1009 patients, 62 (6.1

Triple-negative breast cancer (TNBC) patients often develop resistance to Trop2 antibody-drug conjugate (ADC), and plasmacytoid dendritic cell (pDC) dysfunction is associated with poor prognosis in TNBC, but the underlying mechanism linking these two phenomena remains unclear. The immune cell infiltration and prognosis of TNBC were analyzed through the TIMER database. Sacituzumab Govitecan (SG)-resistant MDA-MB231 cells and xenograft tumor models were established, and the function of pDC was regulated with CpG or anti-BDCA-2. The relationship between Protein arginine methyltransferase 5 (PRMT5) and immune cell infiltration was predicted by the Xiantao academic analysis. CCK-8, plate cloning, EdU and other experiments were used to detect cell functions. The functions of pDC were detected by flow cytometry and ELISA experiments. Besides, IP and IB experiments were implemented to detect the ubiquitination level of interferon regulatory factor 3 (IRF3) and the methylation level of midline 2 (MID2), and the protein interactions were verified through the Co-IP experiment. TNBC tissues resistant to SG showed reduced pDC infiltration and impaired function, associated with downregulation of IRF3. PRMT5 was highly expressed in the cytoplasm of SG-resistant TNBC cells and negatively correlated with pDC cell infiltration. PRMT5 promoted MID2 methylation to induce the ubiquitination and degradation of IRF3. Moreover, silencing PRMT5 activated pDCs, reversed CD8+ T cell suppression, and enhanced the sensitivity of drug-resistant TNBC cells to SG in vitro and in vivo. Targeting PRMT5 reshapes the immune microenvironment by restoring pDC function via the MID2-IRF3 axis, providing a promising strategy to reverse SG resistance in TNBC.

Background: Thyroid cancer incidence is rising worldwide, yet comprehensive longitudinal data linking contemporary demographic, pathological, and surgical trends to recurrence risk remain scarce. Methods: A retrospective analysis was performed on 9504 thyroid cancer patients from 2008 to 2023. Based on the year of treatment, patients were categorized into 3 groups for comparative assessment. Demographic features, clinical pathological characteristics, surgical approaches, and prognostic outcomes were evaluated. Results: Over the 16-year period, the annual number of new thyroid cancer cases demonstrated a consistent upward trend, with a growing proportion detected through routine health screenings. The male-to-female ratio was 1:2.76, with a gradual increase in male patients. The peak age at diagnosis remained between 30 and 60 years, while the proportion of juvenile patients declined steadily. Papillary thyroid carcinoma constituted the predominant histologic type. Surgical management shifted toward more conservative approaches. Although tumor size decreased over time, the incidence of multifocal lesions and the BRAF V600E mutation rate rose. Lymph node metastasis rates also increased, particularly in patients with central region metastases and metastases in ≤5 lymph nodes. Multivariate analysis identified age, tumor size, and number of metastatic lymph nodes as independent risk factors for recurrence in papillary thyroid carcinoma. Patients older than 55 years, those with larger lesions, or those with more lymph node metastases exhibited a significantly elevated recurrence risk. Conclusion: Although thyroid cancers are being detected at earlier stages and smaller sizes, the burdens of molecular, multifocal, and lymph node disease are increasing. Age, tumor size, and nodal metastatic load constitute robust independent predictors of recurrence in papillary thyroid carcinoma, informing risk-adapted surveillance and surgical strategies.

Despite being an option for high-risk or inoperable cases, existing neoadjuvant therapies for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer yield suboptimal pathological responses, necessitating novel strategies. This prospective, phase II ACNTBC trial (NCT05558722) investigated the efficacy and safety of combining anlotinib with chemotherapy as a neoadjuvant treatment for HR+/HER2- breast cancer. Enrolled patients received 5 cycles of anlotinib (12 mg qd, d1‒14; q3w) plus 6 cycles of nab-paclitaxel (200 mg/m2, q3w), pirarubicin (50 mg/m2, q3w), and cyclophosphamide (500 mg/m2, q3w). The primary endpoint was the total pathological complete response (tpCR) rate, with the major secondary endpoints including residual cancer burden (RCB) 0/I rate, objective response rate (ORR), and safety. The study enrolled 31 patients, and the ORR was 93.5% (29/31, 95% CI, 78.6-99.2). In the per-protocol set of 28 patients completing treatment and surgery, the tpCR rate was 14.3% (4/28, 95% CI, 4.0-32.7), with RCB 0/I rate of 25.0% (7/28, 95% CI, 10.7-44.9). Grade 3/4 adverse events included hematologic toxicities, hypertension, proteinuria, and headache, all manageable. Post-hoc biomarker analysis showed that high baseline VEGFR2 expression and microvessel density (MVD) were significantly associated with superior efficacy, and the treatment significantly reduced Ki-67 index, VEGFR2 expression, and MVD. Supporting evidence from an exploratory inverse probability of treatment weighting (IPTW) analysis using a real-world cohort receiving chemotherapy alone indicated a potential benefit of the combination over chemotherapy alone. In conclusion, neoadjuvant anlotinib plus chemotherapy demonstrates promising efficacy and manageable safety in HR+/HER2- breast cancer with a high Ki-67 index.

Background:Cell-in-cell structures (CICs), a novel biomarker for complex cellular interactions, have garnered increasing attention for their potential in predicting cancer patient prognosis. However, the prognostic significance of CICs in tumor outcomes remains inconclusive. To address this, we conducted a meta-analysis to assess the prognostic value of CICs in solid tumors, adhering to the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. Methods:PubMed, Web of Science, and Cochrane Library databases were searched up to October 2024 for the retrieval of full articles. Studies related to the prognosis of cell-in-cell and solid tumors were considered eligible for analysis. The quality of the included studies was assessed according to the National Institute for Health and Clinical Excellence (NICE) Quality assessment tool. Results:We included 1836 patients with solid tumors to evaluate the association between overall cell-in-cell structures (oCICs) and prognosis, and 429 patients to evaluate the association between four subtypes of CICs (tumor-in-tumor [TiT], tumor-in-macrophage [TiM], macrophage-in-tumor [MiT], and lymphocyte-in-tumor [LiT]) and prognosis. We present the hazard ratio (HR) for overall survival (OS) for the number of CICs for each solid tumor. The combined HR for OS of oCICs was 1.64 (95% CI, 1.18-2.28; p = 0.003), and for LiT, it was 1.43 (95% CI, 1.12-1.83; p = 0.005), indicating that both oCICs and LiT are reliable prognostic factors for solid tumors. However, the combined HRs for OS of TiT, TiM, and MiT were 0.72 (95% CI, 0.35-1.48; p = 0.37), 1.28 (95% CI, 0.67-2.45; p = 0.46), and 1.54 (95% CI, 0.93-2.56; p = 0.09), respectively, suggesting that these subtypes may not be reliable prognostic factors due to the limited number of studies. Conclusion:The presence of higher numbers of oCICs and LiT is an adverse prognostic factor for patients and affects OS.

Abstract Immunotherapy has gained approval for use in small cell lung cancer (SCLC), yet only a subset of patients (10–20%) experience meaningful benefits, underscoring the urgent need for more effective therapeutic approaches. This work discovers a distinct HDAC7‐high SCLC phenotype characterized by enhanced proliferative potential, which recurs across various subtypes and serves as a predictor of poorer survival outcomes. By analyzing public datasets, this work finds a strong correlation between c‐Myc and HDAC7. RNA sequencing and cellular experiments show that XPO1 is a key regulator in the HDAC7/c‐Myc axis. HDAC7 promotes β‐catenin deacetylation, phosphorylation modulation, nuclear translocation, and formation of the β‐catenin/TCF/LEF1 complex, which binds to c‐Myc and XPO1 promoters. Activation of the HDAC7/β‐catenin pathway upregulates c‐Myc and XPO1 expression, while c‐Myc also boosts XPO1 expression. Given the difficulty in targeting c‐Myc directly, this work tests selinexor and vorinostat in SCLC xenograft models, with selinexor showing superior results. High HDAC7 expression is linked to increased SCLC proliferation, poorer prognosis, and enhanced sensitivity to selinexor in SCLC cell lines and organoid models. Collectively, this work uncovers a novel HDAC7/c‐Myc/XPO1 signaling axis that promotes SCLC progression, suggesting that HDAC7 may warrant further investigation as a potential biomarker for assessing selinexor sensitivity in SCLC patients.

BACKGROUND:Kruppel-like factor 13 (KLF13) influences both immune system disorders and cancer progression, whereas the effects of KLF13 on the immune escape and breast cancer remain incompletely understood. RESEARCH DESIGN AND METHODS:KLF13 expression was assessed in breast cancer tumor tissues. The roles of KLF13 in cell proliferation, migration, and immune evasion were assessed. RNA sequencing was used to identify the differentially expressed genes and signaling. Chip-seq and luciferase assays were performed to validate binding of KLF13 to its downstream genes. In vivo studies were conducted to confirm the function of KLF13. The mechanisms were elucidated using recovery assays. RESULTS:KLF13 levels were higher in breast cancer tissue. Silencing KLF13 markedly diminished cell proliferation, migration, mammosphere formation, and immune evasion by suppressing the levels of HTRA1 and the Hedgehog signaling pathway. KLF13 overexpression potentiated breast cancer aggressiveness and enhanced immune evasion. Inhibiting KLF13 delayed development of cancer xenografts, as well as curtailing tumor growth, which were reversed by co-expression of HTRA1. Clinical relevance results suggested a positive correlation between KLF13, HTRA1 and density of CD8T cells in human breast cancer patients. CONCLUSIONS:KLF13 can serve as a tumor promoter in breast cancer by influencing HTRA1 and the Hedgehog signaling pathway.

Purpose:Zinc homeostasis and zinc transporter (ZHT) have been closely associated with the development of various cancers. Therefore, in this study, prognostic genes and their mechanisms related to ZHT in breast cancer (BC) were explored. Patients and methods:Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were utilized to identify genes associated with Zinc homeostasis and Zinc transporter-related genes (ZHTGs) in BC. Subsequently, independent prognostic factors and their correlations with clinical features were examined to investigate their association with the prognosis of BC. Finally, we further explored the pathways and immune cells associated with BC prognosis. We also verified gene expression in tissues and cells by quantitative polymerase chain reaction (qPCR). Results:In this study, six prognostic genes were identified. Patients were subsequently classified into high-risk and low-risk cohorts based on the median risk score, with the low-risk group presenting superior survival outcomes. Subsequently, riskScore, age, tumor/node/metastasis (T/N/M) stage showed significant associations with the prognosis of BC, and the constructed nomogram demonstrated strong predictive performance. Clinical analysis revealed differences in risk scores among sub-cohorts with different clinical characteristics, such as race (white and others) and T-stage (T1 and T2, T1 and T3). Furthermore, significant disparities were noted in immune cells and immune checkpoints across different risk cohorts. The results of reverse transcription quantitative PCR were basically consistent with the prediction. In addition, the IHC results from the Human Protein Atlas database further validated our prediction. Conclusion:We screened six prognosis genes related to ZHT in BC, providing a reference for the prognosis and personalized treatment of BC.

Myotubularin-related protein 7 (MTMR7) represses proliferation in several cell types. However, the role of MTMR7 in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary hypertension (PH) is unknown. The present study aimed to explore the role of MTMR7 in PH, as well as in the proliferation and migration of PASMCs. A monocrotaline (MCT)-induced PH mouse model was established. Mtmr7-transgenic (Mtmr7-Tg) mice and an adenovirus carrying the Mtmr7 vector (Ad-Mtmr7) were used to achieve MTMR7 overexpression in vivo and in vitro, respectively. Ultrasound and morphological analyses were used to evaluate the severity of PH. Cell counting kit-8 (CCK-8) and Ki-67 immunofluorescence staining were used to assess the proliferation of PASMCs. Wound-healing and transwell assays were used to assess cell migration. MTMR7 was upregulated in hypoxia-stimulated PASMCs and pulmonary arteries of MCT-treated mice. When compared with wild-type mice, PH-associated symptoms were significantly ameliorated in Mtmr7-Tg mice after MCT treatment when compared to wild-type mice. MTMR7 overexpression suppressed the proliferation and migration of PASMCs induced by hypoxia. Further experiments revealed that MTMR7 inhibited the phosphorylation levels of ERK1/2 and STAT3 both in vivo and in vitro. Restoring either ERK1/2 or STAT3 eliminated the protective role of MTMR7 against PH. Additionally, restoring ERK1/2 also reversed MTMR7-mediated STAT3 dephosphorylation. Our study highlights the inhibitory role of MTMR7 in PH and in the proliferation and migration of PASMCs and thus provides a novel potent therapeutic strategy for treating PH.

Background Malignant hyperthermia is a critical complication that arises when certain anesthetics are administered to susceptible patients, posing a significant risk of mortality if not promptly identified and treated. Case presentation We present a case of a 48-year-old male admitted for the excision of an intracranial tumor. The patient underwent orotracheal intubation under total intravenous anesthesia and non-depolarizing muscle relaxants. After intubation, anesthetic maintenance was achieved through the administration of sevoflurane and intravenous agents. During the initial stage, there was a gradual increase in the patient’s heart rate and end-tidal carbon dioxide pressure (PetCO2). Five hours after anesthesia, sevoflurane administration was ceased, resulting in effective control of the condition. However, a subsequent episode of elevated blood pressure led to the re-administration of sevoflurane, causing a sharp rise in heart rate, PetCO2 levels, and body temperature. The patient’s oropharynx temperature peaked at 39.4 ℃, axillary temperature at 45.1 ℃, PetCO2 level at 69 mmHg, and heart rate at 115 bpm. Due to no dantrolene, we used physical cooling through rapid infusion of ice-cold saline, which initiated a downward trend in core temperature, PetCO2 levels, and heart rate within 1 h. Throughout the anesthesia process, no significant acidosis or hyperkalemia was observed. After completion of the surgery, the patient was admitted to the ICU with a stabilized oropharynx temperature of 37.8 ℃. Subsequently, the patient experienced febrile symptoms in the following days but was discharged safely on the third postoperative day. Genetic testing revealed homozygous mutations in the RYR1 gene, both in the patient and his son, confirming the occurrence of malignant hyperthermia during the operation. Conclusions This case report details the diagnosis and management of a 48-year-old male patient with a homozygous RYR1 gene mutation who developed delayed malignant hyperthermia (MH) following sevoflurane anesthesia. Despite the absence of the specific antagonist dantrolene, the condition was successfully controlled through active symptomatic management. Postoperative genetic testing further confirmed that both the patient and his son carried the pathogenic RYR1 mutation, definitively establishing their MH susceptibility.

Thyroid cancer is one of the most common endocrine diseases worldwide with phenotypic heterogeneity. Deubiquitinating enzymes (DUBs) participated in ubiquitin (Ub) conjugases-induced signal by removing Ub from the substrates. Dysregulation of DUBs are associated with cancer progression, including thyroid carcinoma. In this review, we outline the main classification and structure of DUBs, the expression of DUBs in thyroid cancer, the association of DUBs with survival, and the possible mechanism of DUBs in thyroid cancer progression. Finally, we summarized the development of USP specific inhibitors, the strategies for designing and identifying selective inhibitors.

Purpose: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The aim of this study is to identify noninvasive biomarkers for early-stage DKD or targets for DKD treatment through the analysis of urinary exosomal miRNA expression profiles in DKD patients. Methods: The urinary exosomes were isolated from type 2 diabetes (T2DM) patients with DKD confirmed by renal biopsy (DKD-Exo). The urinary exosomal miRNAs expression profiles were detected using miRNA sequencing, and differentially expressed miRNAs were verified by real-time quantitative PCR. Target genes of these miRNAs and relevant pathways in DKD were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Human podocytes and renal tubular epithelial cells (TECs) were treated with DKD-Exo to investigate the effects of DKD-Exo on podocyte apoptosis and the epithelial-mesenchymal transition (EMT) of TECs. Results: A total of 40 miRNAs were found to be differentially downregulated, 17 of which were named and 23 were untitled; miR-371a-3p, miR-371a-5p, miR-1260b, miR-222-3p, miR-1224-5p, and miR-1253 were reported in DKD for the first time. GO and KEGG pathway analyses suggest that these target genes are related to cellular apoptosis and renal fibrosis in DKD, and are involved in 135 pathways. In vitro, DKD-Exo induced the apoptosis of podocytes and collagen synthesis in TECs. Conclusion: Our study implies that the urinary DKD-Exo could deliver biological information to podocytes or TECs, which play an important role in pathogenesis of DKD.

Ubiquitin-specific protease 10 (USP10) has emerged as a pivotal yet paradoxical regulator in breast cancer (BC) pathogenesis, exhibiting context-dependent duality as both an oncogenic driver and tumor suppressor. This review synthesizes recent advances in elucidating USP10's mechanistic roles in modulating oncogenic signaling, tumor immunity, and therapeutic resistance, with a central focus on its paradoxical dual regulation. USP10 stabilizes tumor-promoting substrates to drive the malignant phenotypes, while also exerting tumor-suppressive effects. Clinically, USP10 overexpression correlates with aggressive phenotypes and poor prognosis. Therapeutically, USP10 inhibition synergizes with Poly ADP-ribose polymerase (PARP) inhibitors and antibody-drug conjugates (ADCs), effectively suppressing tumor growth in preclinical models. Key challenges include resolving USP10's functional dichotomy across BC subtypes, developing isoform-selective inhibitors, and overcoming resistance mechanisms. Future directions emphasize spatial proteomics to map USP10 interactomes in metastatic niches and genetically engineered models for validating synthetic lethality approaches. Collectively, USP10 represents a promising therapeutic target in BC. Its complex, context-dependent role underscores the need for targeted strategies to exploit its functions for precision oncology.

Germline BRCA (gBRCA) mutations complicate clinical surgery management due to a higher risk of initial breast cancer, as well as increased chances of new primary cancers or local recurrence. In this study, we examined the surgical decisions for individuals carrying gBRCA mutations. In this real world study, 1050 female patients with unilateral operable invasive breast cancer getting gBRCA mutation test were enrolled. Pearson chi-square test, continuous correction chi-square test and Fisher's exact test were used to explored the association between gBRCA mutation and surgery choice appropriately. Germline BRCA1 mutations (gBRCA1mut), Germline BRCA2 mutations (gBRCA2mut) and gBRCA1/2mut were found in 5.1% (54/1050), 4.9% (51/1050), 10.0% (105/1050) BC patients separately. Among all patients, those with gBRCAsmut preferred contralateral prophylactic mastectomy than those without mutation (9.3% gBRCA1mut patients compared with 2.0% gBRCA1wt patients, 7.8% gBRCA2mut patients compared with 2.1% gBRCA2wt patients, 8.6% gBRCA1/2mut patients compared with 1.7% gBRCA1/2wt patients, all p<0.05). This tendency could also be found in early-stage BC patients (n=699). While in young (≤40) BC patients (n=346), there were no significant differences in choice between gBRCAsmut cohort and gBRCAswt cohort. Though in all patients, the selection of specific surgery [breast-conserving surgery (BCS), mastectomy or reconstruction surgery] was not affected by gBRCAs mutations. In young BC patients, patients with gBRCA2mut were more likely to choose mastectomy or reconstruction surgery rather than BCS (10.3% gBRCA2mut patients selected BCS compared with 34.4% gBRCA2wt patients, p=0.011). The same tendency could also be found in early-stage BC patients though the difference was not statistically significant (p=0.074). The gBRCA1 mutation had no influence on the specific option. Northwest Chinese BC patients made their surgery choice under the influence of gBRCA1/2 mutation. gBRCA2mut played an more crucial role on it. Ting Wang, Jing Fan, Jiajun Ding, Jing Kong, Mengxuan Li, Yidi Wang, Huimin Meng, Haoyi Zi, Qingxia Li, Shuai Wang, Fei Yao, Changbing Zhu. Impact of gBRCAs mutation on the surgery decisions of Chinese breast cancer (BC) patients: a single-center real world study in Xijing Hospital, Northwest China [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3394.

DEAD-box RNA helicase 17 (DDX17), a key member of the DEAD-box family, is vital in cellular physiological processes. This review summarizes its structural properties, distribution, functions, disease associations, and research trends. Structurally, DDX17 has a conserved DEAD-box domain with RNA-dependent ATPase and helicase activities, producing p72 and p82 isoforms. It distributes in the nucleus and cytoplasm, highly expressed in cardiomyocytes and neuronal tissues. Functionally, DDX17 regulates RNA metabolism, DNA repair, and protein interactions. It is linked to chronic non-infectious diseases: promoting tumor progression via pathways like Wnt/β-catenin; protecting myocardial function in cardiovascular diseases; and involving in neurological disorders.This review provides insights for exploring its biological functions and clinical applications.

BackgroundUveal melanoma (UM) is a common intraocular malignancy in adults frequently with metastasis and poor survival.ObjectiveThis study aimed to identify genes, pathways and the ceRNA axes related to the metastasis of UM.MethodsThe GSE73652 dataset was downloaded and 1719 differentially expressed RNAs (DE-RNAs), including 13 lncRNAs, 5 miRNAs, and 1701 genes, were identified in metastatic UM samples compared with non-metastatic ones.ResultsA total of 11 lncRNA-miRNA pairs were identified by interviewing the DIANA-LncBase database. In addition, 49 UM-related KEGG pathways were filtered in CTD with the search term "uveal melanoma". KEGG pathways involving the differentially expressed genes (DEGs) among the miRNA targets were found and overlapped with UM-related pathways. Accordingly, two crucial overlapped pathways (Wnt and Chemokine signaling pathway) in UM metastasis were mediated by axes consisting of 6 lncRNAs (such as H19, PVT1 and SNGHG1), 3 miRNAs (including hsa-miR-1228, hsa-miR-106b and hsa-miR-6836) and 12 mRNAs (including CTNNB1, MAP3K7, WNT7B, MAPK10 and PLCB4).ConclusionThe results showed that the involvement of UM-related Wnt/β-catenin and Chemokine signaling pathways and the ceRNA regulatory axes showed noteworthy interest in UM metastasis.

Background: Surgical excision of tumors near the lacrimal punctum presents challenges due to the risk of damaging the lacrimal duct, leading to chronic epiphora. Effective reconstruction is essential to preserve lacrimal function and maintain esthetic outcomes. This study discusses the short- to mid-term results of nine cases using conjunctival flap transposition and artificial lacrimal duct placement for repair, considering the duct's anatomical and functional aspects. Case Report: We report on nine patients with benign lesions involving the lacrimal punctum at our hospital from August 2019 to September 2022. A conjunctival flap with a reasonable design based on the defect area was used to cover the defect, and double-tube placement of artificial lacrimal ducts was performed along with suturing of the remaining lacrimal point and lacrimal canaliculus epithelium. Pathological examination of all nine patients after surgery showed "melanocytic nevus." The conjunctival flap survived in the first phase, the lacrimal point remained unblocked, there were no abnormalities in the lower eyelid or medial canthus, the appearance was aesthetically pleasing, lacrimal duct irrigation was unobstructed, and there was no tearing after surgery. All patients were followed up for more than 1 year, and no tumor recurrence or obstruction in the lacrimal duct was observed. Conclusions: Conjunctival flap transposition and artificial lacrimal duct placement is an effective surgical approach for the repair of defects following lacrimal punctum tumor excision. The method not only preserves lacrimal duct function but also achieves satisfactory esthetic results, making it a reliable choice for clinical application.

The identification as well as the interpretation of germline BRCA1 (gBRCA1) and germline BRCA2 (gBRCA2) variants are becoming increasingly critical in the treatment of breast cancer (BC), particularly in cases of hormone receptor-positive BC (HR+ BC). However, a thorough analysis of these variants within the HR+ BC population is still insufficient. In this single-center retrospective study, a total of 1033 female invasive BC patients getting gBRCAs mutation testing with signatures were enrolled, and 652 of them were HR+ BC patients. Pearson chi-square test and continuous correction chi-square test were used to explored the association between gBRCAs mutation and the characteristics of BC. Then clinical and pathological characteristics related to gBRCAs mutation enrollment on univariate logistic regression were selected for multivariate logistic regression. Overall, 108 Luminal A (LA) BC patients, 411 Luminal B represented HER2 negative (LB-HER2-) BC patients, 133 triple-positive BC (TPBC) patients, 109 HER2 positive (HER2+) patients as well as 272 triple-negative BC (TNBC) patients were enrolled in the study. There were 5.6% (58/1033) patients, 4.7% (49/1033) patients and 10.4% (107/1033) patients carrying BRCA1mut, BRCA2mut and BRCA1/2mut individually. As for HR+ patients, the rates were 2.6% (17/652), 5.2% (34/652) and 7.8% (51/652) respectively. It was the most frequent to found gBRCA1mut in TNBC (14.7% in TNBC compared to 2.36% in non-TNBC, p<0.001) while for gBRCA2mut, it was LB-HER2- BC (6.8% in LB-HER2- BC compared to 3.4% in others). Even if in HR+ BC patients, the rate of gBRCA1mut was higher in ER-low patients compared that in ER-high ones (10.5% vs. 1.8%, p<0.001), while this phenomenon could not be found for gBRCA2 mutation. According to the multivariate logistic regression in overall patients, those with bilateral BC (p=0.007) and PR negative BC (p=0.026) were more likely to be BRCA1mut. Though the difference without statistically significant, it seemed that patients younger than 40 (≤40) (p=0.075) and grade III (p=0.056) tended to be gBRCAmut. While patients ≤40 (p=0.008), in T3 or T4 stage (p=0.034) with higher Ki-67 (p=0.015) were more frequent to be BRCA2mut. Among LB-HER2- patients ≤40 in T3 or T4 stage, the rate of gBRCA2mut increased to 26.9% (7/26), no less than the rate of gBRCA1mut in young TNBC patients (24.7%, 20/81), who were recommended the gBRCAs testing. The clinical and pathological characteristics differed in gBRCA1mut and gBRCA2mut among HR-positive BC patients. The screening for gBRCA2 mutation could be meaningful in young LB-HER2- patients with tumor in T3 or T4 stage. Jiajun Ding, Ting Wang, Jing Fan, Huimin Meng, Mengxuan Li, Haoyi Zi, Shuai Wang, Qingxia Li, Yidi Wang, Jing Kong, Fei Yao, Changbing Zhu. Comprehensive profiling of gBRCA1 and gBRCA2 variants in Hormone receptor-positive breast cancer of Chinese patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3384.