Efficacy and safety of pyrotinib combined with albumin-bound paclitaxel as first-line treatment for HER2-positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single-arm, phase 2 prospective clinical trial.

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Functional mechanism of hypoxia-like conditions mediating resistance to ferroptosis in cervical cancer cells by regulating KDM4A SUMOylation and the SLC7A11/GPX4 pathway.

The discovery of ferroptosis has unveiled new perspectives for cervical cancer (CC) management. We elucidated the functional mechanism of hypoxia-like conditions in CC cell ferroptosis resistance. CC cells were subjected to normoxia or hypoxia-like conditions, followed by erastin treatment to induce ferroptosis. The assessment of cell viability/ferroptosis resistance was performed by MTT assay/Fe2+, MDA, and glutathione measurement by colorimetry. KDM4A/SUMO1/Ubc9/SENP1 protein levels were determined by Western blot. Interaction and binding sites between KDM4A and SUMO1 were analyzed and predicted by immunofluorescence/co-immunoprecipitation and GPS-SUMO 1.0 software, with the target relationship verified by mutation experiment. SLC7A11/GPX4/H3K9me3 protein levels, and H3K9me3 level in the SLC7A11 gene promoter region were determined by RT-qPCR and Western blot/chromatin immunoprecipitation. H3H9me3/SLC7A11/GPX4 level alterations, and ferroptosis resistance after KDM4A silencing or KDM4A K471 mutation were assessed. Hypoxia-like conditions increased CC cell ferroptosis resistance and KDM4A, SUMO1, and Ubc9 protein levels, while it decreased SENP1 protein level. KDM4A and SUMO1 were co-localized in the nucleus, and hypoxia-like conditions promoted their interaction. Specifically, the K471 locus of KDM4A was the main locus for SUMO1ylation. Hypoxia-like conditions up-regulated SLC7A11 and GPX4 expression levels and decreased H3K9me3 protein level and H3K9me3 abundance in the SLC7A11 promoter region. KDM4A silencing or K471 locus mutation resulted in weakened interaction between KDM4A and SUMO1, elevated H3K9me3 levels, decreased SLC7A11 expression, ultimately, a reduced CC cell ferroptosis resistance. CoCl2-stimulated hypoxia-like conditions enhanced SUMO1 modification of KDM4A at the K471 locus specifically, repressed H3K9me3 levels, and up-regulated SLC7A11/GPX4 to enhance CC cell ferroptosis resistance.

Effectiveness and Safety of Pyrotinib-Based Therapy in the Treatment of HER2-Positive Breast Cancer Patients with Brain Metastases: A Multicenter Real-World Study.

BACKGROUND: Approximately 30% to 50% of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer develop brain metastasis (BMs). Pyrotinib has shown promising efficacy in these patients. However, real-world evidence supporting its use is scarce. Therefore, we evaluate the efficacy and safety of pyrotinib-based regimens in the real world. MATERIALS AND METHODS: We enrolled patients with BMs from various healthcare facilities in China's Shandong region and used an updated breast-graded prognostic assessment (breast-GPA) to predict survival outcomes. RESULTS: Efficacy and toxicity were assessed in 101 patients. Overall, the median progression-free survival (PFS) was 11.0 months (95% CI, 7.6-14.4 months). PFS was shorter in patients with a breast-GPA of 0 to 2.0 (P< .001). Previous treatment with pertuzumab plus trastuzumab (P = .039) and varying numbers of BMs (P = .028) had a significant positive correlation with PFS. Additionally, radiotherapy (P = .033) for BMs, especially pyrotinib concurrent with radiotherapy (P = .013), significantly prolonged the PFS. In patients with a breast-GPA of 0 to 2.0, a significant difference in PFS was observed depending on whether the brain was the first metastatic site (P< .001). Furthermore, a breast-GPA (0-2.0 vs. 2.5-4.0), and radiotherapy for BMs were found to be independent predictors of PFS. Overall, the objective response rate was 42.6%, while the disease control rate was 88.1%. Diarrhea emerged as the most common adverse event. CONCLUSION: Pyrotinib-based therapy is effective and tolerable in human epidermal growth factor receptor 2-positive metastatic breast cancer with BMs. Patients who underwent radiotherapy for BMs, particularly those who received pyrotinib concurrently with radiotherapy, exhibited a more favorable prognosis.

Rare primary angiitis of the central nervous system affecting the clivus: A case report.

Diseases involving the clivus are highly variable, and the incidence of each disease is rare. Primary central nervous system vasculitis (PACNS) is a rare disease with very heterogeneous clinical manifestations, its diagnosis is often challenging, and histopathology is the gold standard. We report a patient with PACNS of the clivus, with a 1-month history of headache and diplopia, who was misdiagnosed as having a tumor of the clivus during prior treatment, due to computed tomography findings of clivus occupation and bone destruction. Endoscopic resection of the nasal clivus lesions was performed. Pathological examination revealed a small abscess with hemorrhage, necrosis, extensive infiltration of lymphocytes and plasma cells, and granulation tissue scar formation. After histopathological examination, the diagnosis was confirmed, and oral glucocorticoid and cyclophosphamide were commenced. This study is the first to report a tumor-like PACNS, that occurs in the clivus, thereby enriching our understanding of PACNS.

Difference of Antrochoanal Polyps Between Children and Adults in the Chinese Population.

OBJECTIVE: This study aims to find the difference in clinical and immunopathological characteristics between children and adults with antrochoanal polyps (ACPs) in the Chinese population. METHODS: The clinical data of 69 patients diagnosed with ACPs were retrospectively analyzed. Cytokine levels in 16 controls and 40 ACPs tissues were determined by quantitative real-time polymerase chain reaction (qPCR). The expression of matrix metalloproteinase (MMP)-9 was measured using qPCR, immunofluorescent staining, and western blot. RESULTS: There were 51 (73.9%) children (<18 years old) and 18 (26.1%) adults (≥18 years old). The sex ratio differed significantly between the two groups (p = 0.0032). There were no significant differences in the nasal side of ACPs and approaches to surgery between the two groups. In both groups, the most common symptom was nasal obstruction, followed by nasal discharge. As for associated nasal diseases, there was a significant difference between the two groups in septal deviation (p = 0.0223). Adult patients showed significantly higher expression of IL-8 mRNA than children (p = 0.0424). The mRNA and protein levels of MMP-9 were also significantly higher in adult patients than in children (p = 0.0498 and 0.0009, respectively). CONCLUSION: In the Chinese population, the comorbidities and immunopathological characteristics of adult ACP patients are different from those of children. The level of IL-8 and MMP-9 was significantly higher in ACPs of adults than in children, which may contribute to the more severe tissue remolding in adult ACP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2093-2099, 2024.

The metastasis patterns and their prognostic features in patients with de novo metastatic breast cancer of different ages.

PURPOSE: The prognostic outcomes of metastasis patterns in patients with de novo metastatic breast cancer (dnMBC) of different ages are unknown. Our study used a large-scale data to investigate the metastasis patterns and prognostic features in dnMBC of different ages. METHODS: Total 24,698 women with dnMBC in the Surveillance, Epidemiology and End Results database (2010-2018) were divided into three groups by age. Chi-squared test was used to compare metastasis patterns and logistic regression was performed to investigate the risk of age and specific organ metastases. Kaplan-Meier survival curves were used to compare the overall survival. RESULTS: In three groups, young group had the largest proportion of liver metastases (35.2% vs. 28.2% vs. 21.1%, p < 0.001), and elderly group had the largest proportion of lung metastases (22.6% vs. 30.0% vs. 35.0%, p < 0.001) and the lowest proportion of bone metastases (65.7% vs. 67.6% vs. 64.4%, p < 0.001). In young group, patients with liver metastases had better prognosis than patients with lung metastases (MST: 34 months vs. 29 months, p = 0.041), but in middle-aged and elderly groups, the prognosis of lung metastases was better than that of liver metastases (MST in middle-aged group: 24 months vs. 20 months, p = 0.002; MST in elderly group: 12 months vs. 6 months, p < 0.001). CONCLUSION: DnMBC patients at different age have distinct metastasis patterns and prognostic features. The findings lend support to consideration of tailored management and surveillance strategies for different age patients.

Clinical Characteristics of Sphenoid Sinus Fungus Ball: A Nine-year Retrospective Study of 77 Cases.

OBJECTIVE: This study aimed to investigate the clinical characteristics of sphenoid sinus fungus ball (SSFB) to help increase the accuracy of diagnosis and efficiency of treatment. METHODS: We retrospectively analyzed the data of 77 patients who were histopathologically diagnosed with SSFB. RESULTS: The mean age of SSFB patients was 52.4 years (range 25-84), and 47 patients (61.0%) were female. Compared to age-matched and sex-matched chronic rhinosinusitis (CRS) patients, headache was more common in SSFB patients (79.2%; p < 0.0001). SSFB patients also had higher prevalence of diabetes than CRS (p = 0.0420). The features of computed tomography (CT) were sphenoid sinus opacification (100%), sclerosis (93.5%), calcification (76.6%), and bone erosion (41.6%). Functional endoscopic sinus surgery (FESS) was the best treatment option, and the trans-ethmoid (n = 64, 83.1%) was the most commonly used approach. No one experienced a recurrence of SSFB in 44 successfully contacted patients. Six months after FESS, 91.0% of patients (40/44) established proper drainage in the sphenoid sinus. The recovery rates for headache and nasal symptoms were 91.7% (33/36) and 77.8% (7/9) respectively. CONCLUSION: SSFB is more prevalent in older women and usually presents as unilateral headache. Diabetes is a potential risk factor for SSFB. CT findings provide evidence for diagnosis and suggestions for surgical approaches. FESS is the optimal treatment for SSFB. After FESS, most patients had good prognosis with no recurrence of SSFB. However, regular endoscopic follow-up is required due to the possibility of the postoperative closure of sphenoid ostium. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3292-3298, 2023.

Potential predictive value of circulating tumor DNA (ctDNA) mutations for the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer.

Background: In recent years, tumor immunotherapy has become a viable treatment option for triple negative breast cancer (TNBC). Among these, immune checkpoint inhibitors (ICIs) have demonstrated good efficacy in advanced TNBC patients with programmed death-ligand 1 (PD-L1) positive expression. However, only 63% of PD-L1-positive individuals showed any benefit from ICIs. Therefore, finding new predictive biomarkers will aid in identifying patients who are likely to benefit from ICIs. In this study, we used liquid biopsies and next-generation sequencing (NGS) to dynamically detect changes in circulating tumor DNA (ctDNA) in the blood of patients with advanced TNBC treated with ICIs and focused on its potential predictive value. Methods: From May 2018 to October 2020, patients with advanced TNBC treated with ICIs at Shandong Cancer Hospital were included prospectively. Patient blood samples were obtained at the pretreatment baseline, first response evaluation, and disease progression timepoints. Furthermore, 457 cancer-related genes were evaluated by NGS, and patients' ctDNA mutations, gene mutation rates, and other indicators were determined and coupled with clinical data for statistical analysis. Results: A total of 11 TNBC patients were included in this study. The overall objective response rate (ORR) was 27.3%, with a 6.1-month median progression-free survival (PFS) (95% confidence interval: 3.877-8.323 months). Of the 11 baseline blood samples, 48 mutations were found, with the most common mutation types being frame shift indels, synonymous single-nucleotide variations (SNVs), frame indel missenses, splicing, and stop gains. Additionally, univariate Cox regression analysis revealed that advanced TNBC patients with one of 12 mutant genes (CYP2D6 deletion and GNAS, BCL2L1, H3F3C, LAG3, FGF23, CCND2, SESN1, SNHG16, MYC, HLA-E, and MCL1 gain) had a shorter PFS with ICI treatment (p < 0.05). To some extent, dynamic changes of ctDNA might indicate the efficacy of ICIs. Conclusion: Our data indicate that ICI efficacy in patients with advanced TNBC may be predicted by 12 mutant ctDNA genes. Additionally, dynamic alterations in peripheral blood ctDNA might be used to track the effectiveness of ICI therapy in those with advanced TNBC.

Comparative analysis of three common imaging modalities for nasolabial cysts.

OBJECTIVE: To compare the clinical diagnostic value of ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) for nasolabial cysts. METHODS: The clinical and imaging data of 20 patients with 21 nasolabial cysts confirmed surgically and histopathologically were retrospectively analyzed. RESULTS: The largest cyst was 3.4 × 2.7 × 2.3 cm, and the smallest cyst was 1.1 × 0.7 × 0.5 cm. All cysts were located in the soft tissue between the nasolabial fold and maxillary bone. USG showed sensitivity of 95%, accuracy of 95%, and a missed diagnosis rate of 5%; CT showed sensitivity of 80%, accuracy of 80%, and a missed diagnosis rate of 20%; and MRI showed sensitivity of 85%, accuracy of 85%, and a missed diagnosis rate of 15%. CONCLUSIONS: USG showed higher sensitivity and accuracy and a lower missed diagnosis rate than CT and MRI. Therefore, USG is worth popularizing on a large scale for the diagnosis of nasolabial cysts.

Schwannoma in the Olfactory Groove: Two Case Reports.

The occurrence of an isolated schwannoma in the olfactory groove is extremely rare. We herein present 2 cases of schwannomas in the olfactory groove that were treated with endoscopic excision. In these 2 cases, the tumor originated in the cribriform plate and cerebrospinal fluid rhinorrhea occurred after tumor resection, which was repaired using tissue grafts.

Endoscopic nasal surgery for mucocele and pyogenic mucocele of turbinate: Three case reports.

BACKGROUND: Cases of turbinate mucocele or pyogenic mucocele are extremely rare. During nasal endoscopy, turbinate hypertrophy can be detected in patients with turbinate or pyogenic mucocele. However, in many instances, differentiating between turbinate hypertrophy and turbinate mucocele is difficult. Radiological examinations, such as computed tomography (CT) or magnetic resonance imaging (MRI), are essential for the accurate diagnosis of turbinate mucocele. Herein, we report three cases of mucocele or pyogenic mucocele of turbinate, including their clinical presentation, imaging findings, and treatments, to help rhinologists understand this condition better. CASE SUMMARY: Three cases of turbinate and pyogenic mucocele were encountered in our hospital. In all patients, nasal obstruction and headache were the most common symptoms, and physical examination revealed hypertrophic turbinates. On CT scan, mucocele appeared as non-enhancing, homogeneous, hypodense, well-defined, rounded, and expansile lesions. Meanwhile, MRI clearly illustrated the cystic nature of the lesion on T2 sequences. Two patients with inferior turbinate mucocele underwent mucocele lining removal, while the patient with pyogenic mucocele underwent endoscopic middle turbinate marsupialization. The patients were followed up on the first, third, sixth month, and 1 year after discharge, and no complaints of headache and nasal congestion were reported during this period. CONCLUSION: In conclusion, both CT and MRI are helpful in the diagnosis of turbinate or pyogenic mucocele. Additionally, endoscopic nasal surgery is considered to be the most effective treatment method.

Endogenous Stimuli-Responsive Autonomous Separation of Dual-Targeting DNA Guided Missile from Nanospacecraft for Intelligent Targeted Cancer Therapy.

Most conventional chemotherapeutics indiscriminately kill both cancerous and healthy cells and cause toxic side effects, limiting the maximum tolerated dose and thereby compromising therapeutic efficacy. To address this challenge, here dual-targeting intelligent DNA guided missile (GM)-integrated nanospacecraft (NSC) (abbreviated as GM-NSC) is demonstrated for staged chemotherapeutic drug delivery exclusively into cancer cells and then mitochondria (not into healthy cells). GM-NSC is essentially a core/shell nanocomposite composed of gold nanoparticles (AuNPs) surrounded by a high-density multilayer DNA crown that is self-assembled from DNA tetrahedral units (DNA Tetra) in a highly ordered manner. Each tetrahedral structural unit is equipped with three functional components: a cancer cell-targeting aptamer pointing toward the outside environment, a hidden mitochondria-targeting triphenylphosphonium (TPP), and an explosive bolt (E-bolt). GM-NSC can remain intact in fetal bovine serum solution over 12 h and has 53-fold improved systemic stability. Each GM-NSC accommodates 1250 anticancer doxorubicin (Dox), achieving a 48-63-fold improved drug payload capacity. When systemically administrated into a tumor-bearing xenograft murine model, Dox-loaded GM-NSC enters into tumor sites with 18-fold improved specificity followed by autonomous separation of GMs from the NSC core and specific mitochondrial accumulation due to the explosion of E-bolt upon stimuli of endogenous miRNAs. About 80% of Dox uptaken is transferred into mitochondria and induces mitochondria-mediated apoptosis. As a result, the growth of malignant tumor is almost 100% inhibited without detectable toxicity to healthy tissues. Due to the desirable systemic stability, good biocompatibility, high cargo loading capability, satisfactory in vivo biodistribution, and therapeutic efficacy without adverse effects, intelligible GM-NSC is expected to become an alternative drug delivery system for precision cancer therapy.

Design and application of DNA nanostructures for organelle-targeted delivery of anticancer drugs.

INTRODUCTION: DNA nanostructures targeting organelles are of great significance for the early diagnosis and precise therapy of human cancers. This review is expected to promote the development of DNA nanostructure-based cancer treatment with organelle-level precision in the future. AREAS COVERED: In this review, we introduce the different principles for targeting organelles, summarize the progresses in the development of organelle-targeting DNA nanostructures, highlight their advantages and applications in disease treatment, and discuss current challenges and future prospects. EXPERT OPINION: Accurate targeting is a basic problem for effective cancer treatment. However, current DNA nanostructures cannot meet the actual needs. Targeting specific organelles is expected to further improve the therapeutic effect and overcome tumor cell resistance, thereby holding great practical significance for tumor treatment in the clinic. With the deepening of the research on the molecular mechanism of disease development, especially on tumorigenesis and tumor progression, and increasing understanding of the behavior of biological materials in living cells, more versatile DNA nanostructures will be constructed to target subcellular organelles for drug delivery, essentially promoting the early diagnosis of cancers, classification, precise therapy and the estimation of prognosis in the future.

Hairpin allosteric molecular beacons-based cascaded amplification for effective detection of lung cancer-associated microRNA.

Lung cancer with worldwide distribution, high incidence and low survival rate is significantly and increasingly threatening human health. Thus, the specific detection of lung cancer-associated biomarkers is of crucial importance in early diagnosis and treatment. In this work, taking microRNA-21 as an example, a biosensor is proposed via a stimuli-induced strand displacement amplification (SDA) and cascade signal amplification with the assistance of polymerase. An allosteric molecular beacon (MB) with chemical modification is designed to emit the enhanced fluorescent signal in presence of microRNA target. The sensing system possesses a linear calibration curve from 5 pM to 40 nM with the limit of detection (LOD) of 0.7 pM and displays good specificity to discriminate coexisting microRNAs. In addition, the feasibility is confirmed by performing the detection of miRNA-21 extracted from non-small cell lung cancer (NSCLC) A549 cells, and a good recovery is achieved in complex human serum sample. Therefore, the miRNA-triggered cascaded amplification would be crucial strategy to facilitate microRNA analysis in the biological detection and broad clinical applications.

A sensing system constructed by combining a structure-switchable molecular beacon with nicking-enhanced rolling circle amplification for highly sensitive miRNA detection.

The detection of disease-related biomarkers, including microRNA (miRNA), is of crucial importance in reducing the morbidity and mortality of cancer. Thus, there is a great desire to develop an efficient and simple sensing method to fulfill the detection of miRNAs. In this study, a novel amplification assay strategy is demonstrated for the highly sensitive detection of miRNA-21 by combining a structure-switchable molecular beacon with nicking-enhanced rolling circle amplification (SMB-NRCA). A circular padlock probe (CPP) contains a target recognition sequence, two binding sites for nicking endonuclease and three hybridization sites for SMBs. miRNA-21 can hybridize with the CPP and act as polymerization primer that initiates the rolling circle amplification (RCA) reaction and two different nicking-mediated RCA processes, releasing a large amount of SMBs and leading to a significantly amplified fluorescence signal originating from the restoration of pre-quenched fluorescence via their structural switching. Via the signal amplification based on the combination of RCA, nicking and SDA, this assay system can quantitatively detect miRNA-21 in a linear change of three orders of magnitude with a detection limit of 1 pM. The assay specificity is very high so that there is no interference from coexisting miRNAs. Moreover, the sensing system possesses ideal anti-interference ability in complicated milieux such as human serum. The novel sensing strategy shows tremendous prospects for application in tumor diagnosis and clinical therapy guidance.

Hypoxia Enhances HIF1α Transcription Activity by Upregulating KDM4A and Mediating H3K9me3, Thus Inducing Ferroptosis Resistance in Cervical Cancer Cells.

Objective: Cervical cancer (CC) is a prevalent cancer in women. Hypoxia plays a critical role in CC cell ferroptosis resistance. This study explored the mechanism of hypoxia in CC cell ferroptosis resistance by regulating HIF1α/KDM4A/H3K9me3. Methods: Cultured SiHa and Hela cells were exposed to CoCl2 and treated with Erastin. Cell viability was detected by MTT assay, and concentrations of iron ion, MDA and GSH were determined using corresponding kits. Expressions of KDM4A, HIF1α, TfR1, DMT1, and H3k9me3 were detected by RT-qPCR, Western blot, and ChIP assay. The correlation of KDM4A and HIF1α was analyzed on Oncomine, UALCAN, and Starbase. CC cells were co-transfected with shKDM4A or/and pcDNA3.1-HIF1α. Iron uptake and release were assessed using the isotopic tracer method. The binding relationship between HIF1α and HRE sequence was verified by dual-luciferase assay. Results: Cell viability and GSH were decreased while iron concentration, MDA, KDM4A, and HIF1α levels were increased in hypoxia conditions. The 2-h hypoxia induced ferroptosis resistance. KDM4A and HIF1α were highly-expressed in CC tissues and positively correlated with each other. KDM4A knockdown attenuated cell resistance to Erastin, increased H3K9me3 level in the HIF1α promoter region, and downregulated HIF1α transcription and translation. H3K9me3 level was increased in the HIF1α promoter after hypoxia. HIF1α overexpression abrogated the function of KDM4A knockdown on ferroptosis in hypoxia conditions. Iron uptake/release and TfR1/DMT1 levels were increased after hypoxia. Hypoxia activated HRE sequence in TfR1 and DMT1 promoters. Conclusion: Hypoxia upregulated KDM4A, enhanced HIF1α transcription, and activated HRE sequence in TfR1 and DMT1 promoters via H3K9me3, thus inducing ferroptosis resistance in CC cells.

Tumor-targeting [2]catenane-based grid-patterned periodic DNA monolayer array for in vivo theranostic application.

DNA nanotechnology is often used to build various nano-structures for signaling and/or drug delivery, but it essentially suffers from several major limitations, such as a large number of DNA strands and limited targeting ligands. Moreover, there is no report on in vivo two-dimensional DNA arrays because of various technical challenges. By cross-catenating two palindromic DNA rings, herein, we demonstrate a catenane-based grid-patterned periodic DNA monolayer array ([2]GDA) capable of preferentially accumulating in tumor tissues without any targeting ligands, with a thickness equal to the double-helical DNA monolayer (nearly 2 nm). The structural flexibility of [2]GDA enabled it to fold into a spherical object in solution, favoring cellular uptake. Thus, its cellular internalization activity was comparable with that of the commercial lipofectamine 3000. Moreover, [2]GDA retained the structural integrity over 24 h incubation in biological solutions, achieving a 360-fold improvement in in vivo stability. Significantly, anticancer drug-loaded [2]GDA exhibits desirable therapeutic efficacy in tumor-bearing animals without detectable side effects.

Characterization of TiO2 and an as-prepared TiO2/SiO2 composite and their photocatalytic performance for the reduction of low-concentration N-NO3- in water.

Excessive N-NO3- water pollution has become a widespread and serious problem that threatens human and ecosystem health. Here, a TiO2/SiO2 composite photocatalyst was prepared via the sol-gel/hydrothermal method. TiO2 and TiO2/SiO2 were characterized by X-ray diffraction (XRD), UV-Vis differential reflectance spectroscopy (DRS), Fourier infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). Afterward, the photocatalytic performance of TiO2 and TiO2/SiO2 to reduce low nitrate concentrations (30 mgN L-1) under UV light was evaluated and the effects of different factors on this process were investigated, after which the reaction conditions were optimized. Removal rates of up to 99.93% were achieved at a hole scavenger (formic acid) concentration of 0.6 mL L-1, a CO2 flow rate of 0.1 m3 h-1, and a TiO2 concentration of 0.9 g L-1. In contrast, TiO2/SiO2 at a 1.4 g L-1 concentration and a TiO2 load rate of 40% achieved a removal rate of 83.48%, but with more than 98% of nitrogen generation rate. NO2- and NH4+ were the minor products, whereas N2 was the main product.

Survival analysis and nomogram for early-stage occult breast cancer with positive lymph nodes based on the SEER database.

Background: Occult breast cancer (OBC) is a rare type of breast cancer, which accounts for 0.3-1.0% of all breast cancers. However, the treatment of OBC remains controversial, especially the local treatment. We aimed to analyze the impact of different treatment and N stage on survival in early-stage OBC patients, and construct a nomogram to predict the prognosis. Methods: The data of patients with early-stage breast cancer were obtained from 17 registries in the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics and breast cancer-specific survival (BCSS) were compared among the groups. Cox proportional risk models were used for both the univariate and multivariate analyses. Variables with a P value <0.07 in the univariate analysis were included in the multivariate analysis. The independent prognostic factors were included in the nomogram and validated internally. Results: A total of 492 early-stage OBC patients were randomized at a 7:3 ratio into the training cohort (n=348) and the testing cohort (n=144). N2+ stage patients had a worse prognosis than N1 stage patients (P=0.0051). Triple-negative breast cancer (TNBC) patients had the worst prognosis. Early-stage OBC patients benefited from surgery (P=0.0093) and radiotherapy (P=0.0102), but not chemotherapy (P=0.4030). An analysis of OBC patients with different N stages showed that in terms of treatment, N1 stage patients benefited from surgery (P=0.023), but did not benefit significantly from radiotherapy (P=0.0793), whereas N2+ stage patients benefited from radiotherapy (P=0.0098), but the benefit from surgery was not significant (P=0.1005). In the multivariate analysis, N stage, surgery, and radiotherapy remained statistically significant. Based on the results of the multivariate analysis, we constructed a nomogram for estimating the 3- and 5-year BCSS of OBC patients. The concordance index and the calibration plots show that our nomogram had sufficient accuracy and good coordination. Conclusions: N stage, surgery, and radiotherapy were identified as independent prognostic factors for OBC. We successfully constructed a nomogram using these independent risk factors and demonstrated that it could help predict the 3- and 5-year BCSS of OBC patients. Further data analyses need to be conducted to revise the treatment of early-stage OBC.