PARP inhibitor boost the efficacy of photothermal therapy to TNBC through enhanced DNA damage and inhibited homologous recombination repair.

Triple-negative breast cancer (TNBC) could benefit from PARP inhibitors (PARPi) for their frequent defective homologous recombination repair (HR). However, the efficacy of PARPi is limited by their lower bioavailability and high susceptibility to drug resistance, so it often needs to be combined with other treatments. Herein, polydopamine nanoparticles (PDMN) were constructed to load Olaparib (AZD) as two-channel therapeutic nanoplatforms. The PDMN has a homogeneous spherical structure around 100 nm and exhibits a good photothermal conversion efficiency of 62.4%. The obtained AZD-loaded nanoplatform (PDMN-AZD) showed enhanced antitumor effects through the combination of photothermal therapy (PTT) and PARPi. By western blot and flow cytometry, we found that PTT and PARPi could exert synergistic antitumor effects by further increasing DNA double-strand damage (DSBs) and enhancing HR defects. The strongest therapeutic effect of PDMN-AZD was observed in a BRCA-deficient mouse tumor model. In conclusion, the PDMN-AZD nanoplatform designed in this study demonstrated the effectiveness of PTT and PARPi for synergistic treatment of TNBC and preliminarily explained the mechanism.

Rice body synovitis in pediatrics: three different case reports.

Rice body synovitis (RBS) is a rare disease, especially in children. Rheumatoid disorders and tuberculosis are the first two reasons for the formation of the RB. The diagnosis is mainly based on imaging and histopathological features. Herein, we report three cases of RBS in children diagnosed with congenital synovial chondromatosis, tuberculosis (unconfirmed), and ANA -positive juvenile idiopathic arthritis. Clinical features, radiographic findings, pathophysiology, treatment process, and prognosis were reviewed and documented meticulously to enhance cognition in this population and provide some references for clinicians in diagnosing and treating the disease.

Schlafen 11 triggers innate immune responses through its ribonuclease activity upon detection of single-stranded DNA.

Nucleic acids are major structures detected by the innate immune system. Although intracellular single-stranded DNA (ssDNA) accumulates during pathogen infection or disease, it remains unclear whether and how intracellular ssDNA stimulates the innate immune system. Here, we report that intracellular ssDNA triggers cytokine expression and cell death in a CGT motif-dependent manner. We identified Schlafen 11 (SLFN11) as an ssDNA-activated RNase, which is essential for the innate immune responses induced by intracellular ssDNA and adeno-associated virus infection. We found that SLFN11 directly binds ssDNA containing CGT motifs through its carboxyl-terminal domain, translocates to the cytoplasm upon ssDNA recognition, and triggers innate immune responses through its amino-terminal ribonuclease activity that cleaves transfer RNA (tRNA). Mice deficient in Slfn9, a mouse homolog of SLFN11, exhibited resistance to CGT ssDNA-induced inflammation, acute hepatitis, and septic shock. This study identifies CGT ssDNA and SLFN11/9 as a class of immunostimulatory nucleic acids and pattern recognition receptors, respectively, and conceptually couples DNA immune sensing to controlled RNase activation and tRNA cleavage.

Paeonol interferes with lupus nephritis by regulating M1/M2 polarization of macrophages.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology. It is marked by the production of pathogenic autoantibodies and the deposition of immune complexes. Lupus nephritis (LN) is a prevalent and challenging clinical complications of SLE. Cortex Moutan contains paeonol as its main effective component. In this study, using the animal model of SLE induced by R848, it was found that paeonol could alleviate the lupus-like symptoms of lupus mouse model induced by R848 activating TLR7, reduce the mortality and ameliorate the renal damage of mice. In order to explore the mechanism of paeonol on lupus nephritis, we studied the effect of paeonol on the polarization of Raw264.7 macrophages in vitro. The experimental results show that paeonol can inhibit the polarization of macrophages to M1 and promote their polarization to M2, which may be related to the inhibition of MAPK and NF-κB signaling pathways. Our research provides a new insight into paeonol in the treatment of lupus nephritis, which is of great importance for the treatment of systemic lupus erythematosus and its complications.

Burkitt's lymphoma in a young boy progressing to systemic lupus erythematosus during follow-up: a case report and literature review.

Introduction: Patients with systemic lupus erythematosus (SLE) are at a higher risk of developing cancer, particularly hematological malignancies such as lymphoma and leukemia. However, existing studies on this topic that assess cancer incidence following SLE diagnosis are limited. In addition, SLE can be diagnosed after cancer, although such cases in children have been rarely reported. Case report: We present the case of a 2.6-year-old boy who presented to our institute with fever and abdominal pain. His physical examination revealed a periumbilical mass, which was pathologically diagnosed as Burkitt's lymphoma. Autologous stem cell transplantation was performed to consolidate the effect of chemotherapy and reduce the risk of cancer relapse. He was diagnosed with SLE 5 years later, following the presentation of a fever with rash, positive autoantibodies, decreased complement, and kidney involvement. At the final follow-up, the patient was still alive and showed no recurrence of Burkitt's lymphoma or disease activity of SLE. Conclusion: Despite the low frequency of SLE in children with lymphoma, cancer and SLE may be induced by a common mechanism involving B-cell cloning and proliferation. Therefore, hematologists and rheumatologists should be aware of the occurrence of these two conditions during patient follow-up.

Libman-Sacks endocarditis in a child with systemic lupus erythematosus: a case report and literature review.

Libman-Sacks endocarditis (LSE) is a cardiac condition characterized by the growth of verrucous vegetation. Although relatively rare in children, LSE is nevertheless a known cardiac manifestation of autoimmune diseases, including systemic lupus erythematosus (SLE). The mitral valve is the most commonly affected region, followed by the aortic valve, while the tricuspid and pulmonary valves are rarely affected. The management of established Libman-Sacks vegetation poses significant challenges, often necessitating surgical interventions, although surgery is not the primary treatment modality. Herein, we present the case of a 14-year-old Chinese female patient whose initial lupus manifestation included LSE, among other symptoms and signs that provided insights into the final diagnosis of SLE. After early comprehensive pharmacological treatment, tricuspid regurgitation and vegetation disappeared within 28 days without necessitating cardiac surgery, indicating that the resolution of LSE vegetation in this patient was achieved through a combination of immunosuppressive and anticoagulant therapy. These findings suggest the potential of this treatment approach as a viable model for the management of LSE in young patients.

Suppression of ZNF205-AS1/EGR4 positive feedback loop attenuates cisplatin resistance of non-small cell lung cancer cells via targeting miR-138-5p/OCT4 pathway.

Background: Long non-coding RNAs (lncRNAs) are frequently reported to involve in the onset and development of non-small cell lung cancer (NSCLC). Cisplatin (DDP) resistance continues to pose a daunting challenge for improving the prognosis of NSCLC patients. The current study intends to elucidate the molecular mechanisms underlying the function of lncRNA ZNF205 AS1/early growth response 4 (EGR4) positive feedback loop in DDP resistance of NSCLC. Methods: A series of assays, including real-time polymerase chain reaction (PCR), western blotting, flow cytometry, and dual-luciferase reporter, were performed to evaluate the effect of ZNF205-AS1/EGR4 loop in the established DDP-resistant A549 cell line and its progenitor A549 cell line. Immunohistochemistry (IHC) technique was conducted to investigate the expression pattern of EGR4 and octamer-binding protein 4 (OCT4) in NSCLC tissues. RNA pull-down assay was carried out to evaluate the interaction between miR-138-5p and EGR4 and OCT4. Transwell assay and wound healing assay was used to evaluate the invasive and migratory potential of cells subject to various treatment. The protein levels of Bcl2, Bax, Cl-caspase 3, Cl-PARP and OCT4 were measured in western blotting assay. Results: The levels of ZNF205-AS1, EGR4 and OCT4 were notably upregulated in post-chemotherapy DDP-resistant lung specimens, as opposed to those pre-chemotherapy, and in A549/DDP cells than the progenitor DDP-sensitive A549 cells. In contrast, the level of miR-138-5p was significantly reduced in A549/DDP cells (P<0.05). Luciferase reporter assay confirmed the interaction between ZNF205-AS1 and miRNA-138-5p. Protein-RNA interaction was validated between miR-138-5p, EGR4 and OCT4. The higher chemosensitivity of DDP-resistant cells induced by the loss-of-function of ZNF205-AS1 could be diminished by a miR-138-5p inhibitor. Conclusions: Our data demonstrated that miR-138-5p/OCT4 functions as a downstream effector of the ZNF205-AS1/EGR4 positive feedback loop and mediates resistance of NSCLC cells to DDP. Our work sheds light on the therapeutic strategies for NSCLC with DDP chemoresistance.

Computationally Designed Small Molecules Disassemble Both Soluble Oligomers and Protofibrils of Amyloid ß-Protein Responsible for Alzheimer's Disease.

Alzheimer's disease (AD) is one of the world's most pressing health crises. AD is an incurable disease affecting more than 6.5 million Americans, predominantly the elderly, and in its later stages, leads to memory loss, dementia, and death. Amyloid ß (Aß) protein aggregates have been one of the pathological hallmarks of AD since its initial characterization. The early stages of Aß accumulation and aggregation involve the formation of oligomers, which are considered neurotoxic and play a key role in further aggregation into fibrils that eventually appear in the brain as amyloid plaques. We have recently shown by combining ion mobility mass spectrometry (IM-MS) and atomic force microscopy (AFM) that Aß42 rapidly forms dodecamers (12-mers) as the terminal oligomeric state, and these dodecamers seed the early formation of Aß42 protofibrils. The link between soluble oligomers and fibril formation is one of the essential aspects for understanding the root cause of the disease state and is critical to developing therapeutic interventions. Utilizing a joint pharmacophore space (JPS) method, potential drugs have been designed specifically for amyloid-related diseases. These small molecules were generated based on crucial chemical features necessary for target selectivity. In this paper, we utilize our combined IM-MS and AFM methods to investigate the impact of three second-generation JPS small-molecule inhibitors, AC0201, AC0202, and AC0203, on dodecamer as well as fibril formation in Aß42. Our results indicate that AC0201 works well as an inhibitor and remodeler of both dodecamers and fibril formation, AC0203 behaves less efficiently, and AC0202 is ineffective.

A Novel "Inside-Out" Intraocular Nanomedicine Delivery Mode for Nanomaterials' Biological Effect Enhanced Choroidal Neovascularization Occlusion and Microenvironment Regulation.

Photodynamic therapy (PDT) is commonly used in choroidal neovascularization (CNV) treatment due to the superior light transmittance of the eye. However, PDT often leads to surrounding tissue damage and further microenvironmental deterioration, including exacerbated hypoxia, inflammation, and secondary neovascularization. In this work, Pt nanoparticles (NPs) and Au NPs decorated zeolitic imidazolate framework-8 nanoplatform is developed to load indocyanine green for precise PDT and microenvironment amelioration, which can penetrate the internal limiting membrane through Müller cells endocytosis and target to CNV by surface-grafted cyclo(Arg-Gly-Asp-d-Phe-Lys) after intravitreal injection. The excessive H2 O2 in the CNV microenvironment is catalyzed by catalase-like Pt NPs for hypoxia relief and enhanced PDT occlusion of neovascular. Meanwhile, Au NPs show significant anti-inflammatory and anti-angiogenesis properties in regulating macrophages and blocking vascular endothelial growth factor (VEGF). Compared with verteporfin treatment, the mRNA expressions of hypoxia-inducible factor-1α and VEGF in the nanoplatform group are downregulated by 90.2% and 81.7%, respectively. Therefore, the nanoplatform realizes a comprehensive CNV treatment effect based on the high drug loading capacity and biosafety. The CNV treatment mode developed in this work provides a valuable reference for treating other diseases with similar physiological barriers that limit drug delivery and similar microenvironment.

Intensity modulated radiation therapy for elderly patients with esophageal cancer: Our experience.

The aim of this study was to discuss the treatment mode of radical radiotherapy for elderly patients with esophageal cancer. The clinical data of 136 elderly patients (≥60 years old) with esophageal cancer (EC) who received radical intensity-modulated radiotherapy in the Second Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2019 were retrospectively analyzed. Cox risk model was used for multivariate prognostic analysis, and Kaplan Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Cox regression analysis showed that ECOG score, basic diseases, T stage, radiation dose, radiation injury and chemotherapy were the prognostic factors of elderly patients. The median OS of the radiotherapy group, concurrent chemoradiotherapy group and sequential chemoradiotherapy group were 17, 41 and 10 months (p=0.009), respectively. The 3-year OS and PFS of concurrent intravenous chemotherapy and oral chemotherapy were 50%, 42.9% and 34.1%, 28.6% (p=0.641, p=0.702), respectively. The median OS of IFI and ENI were 23 and 24 months (p=0.219) and the local recurrence rate were 59.8% and 43.2% (p=0.069), respectively, but the incidence and mortality of radiation pneumonia and esophagitis in ENI were higher. The 3-year OS and PFS the low-dose group (≤60Gy) and high-dose group (>60Gy) were 19.1%, 40.4% and 14.9%, 29.2% (p=0.012, p=0.049), respectively. In conclusion, for elderly patients with inoperable EC, radical chemoradiotherapy should be considered a preferable selection. Among them, oral drugs and high-dose involved field irradiation exhibited better curative effects and safety.

Kikuchi-Fujimoto disease as the initial manifestation of systemic lupus erythematosus complicated with macrophage activation syndrome: two case reports and a review of literature.

BACKGROUND: Kikuchi-Fujimoto disease (KFD) is a self-limiting and benign disease characterized by cervical lymphadenopathy and fever. Although KFD should be made differentially diagnosed from infectious, autoimmune, and malignant diseases, it sometimes occurs in patients with systemic lupus erythematosus (SLE) and can be complicated with macrophage activation syndrome (MAS). However, it is rare that KFD is the initial manifestation of SLE and to be complicated with MAS. CASE PRESENTATION: A 9.6-year-old girl presented with high-grade fever, double-side cervical lymphadenopathy with mild pain of one week, leukopenia, alopecia, and rash on the cheek. During hospitalization, laboratory investigations showed positive antinuclear antibody (ANA), low complement 3 (C3), and low complement 4 (C4). Imaging investigations showed pleural and pericardial effusion. A 10.3-year-old girl presented with intermittent high-grade fever, double-sided cervical lymphadenopathy with obvious pain of 1-month duration, and discoid lesion on the cheek. During hospitalization, laboratory investigations showed positive ANA, leukopenia, thrombocytopenia, anemia with positive Coombs' test, low C3, and positive Smith antibodies. Both cases were diagnosed with KFD using lymph node biopsy, simultaneously fulfilling the diagnostic criteria of SLE. Subsequently, the two girls became complicated with MAS, followed by interstitial lung disease and neuropsychiatric lupus, respectively. Both patients benefited from high-dose methylprednisolone pulse therapy combined with intravenous cyclophosphamide. CONCLUSIONS: More attention should be paid to differential diagnosis, especially SLE, in children diagnosed with KFD. In addition, children with SLE who presented with KFD as the initial manifestation seem to have a higher risk of developing MAS and experiencing organ involvement.

Hypoxia upregulates the expression of lncRNA H19 in non-small cell lung cancer cells and induces drug resistance.

Background: The incidence of lung cancer is extremely high. For treatment, the chemotherapy of lung cancer is low, and drug resistance and recurrence are frequently observed, in which hypoxic tumor microenvironments play a key role. We investigated the upregulation of long non-coding ribonucleic acid (lncRNA) H19 expression and the induction of drug resistance in non-small cell lung cancer (NSCLC) cells under hypoxic conditions. Methods: We used cobaltous chloride (CoCl2) to create hypoxic culture environments for the A549 and H1650 cells, and they were divided into normoxia and hypoxia groups. We used real-time quantitative PCR detecting system (qPCR) to detect the messenger RNA (mRNA) expressions of lncRNA H19, hypoxia-inducible factor 1-α (HIF1-α), multi-drug resistant associated protein 1 (MRP1), and heme oxygenase-1 (HO-1), and western blot to detect the protein expressions of HIF1-α, MRP1, HO-1, and P-glycoprotein (P-gp). We performed cell migration and invasion assays. Annexin V-Allophycocyanin (APC) and flow cytometry were used to detect the apoptotic rates. Results: We found that the expression levels of lncRNA H19, HIF1-α, HO-1, multi-drug resistant associated protein 1 (MRP1), and P-glycoprotein increased significantly in the NSCLC cell lines (A549 and H1650) under hypoxic conditions, as determined by the qPCR and western blot analyses. In NSCLC cells cultured under hypoxic conditions, the invasion and migration ability of tumor cells increased significantly, resistance to cisplatin increased, and cisplatin-induced apoptosis decreased considerably. In addition, chemoresistance was also induced in tumor cells under hypoxic conditions. Conclusions: These results indicate that hypoxia increased the expression levels of lncRNA H19 and induced chemoresistance in tumor cells.

Concurrent chemoradiotherapy using gemcitabine and nedaplatin in recurrent or locally advanced head and neck squamous cell carcinoma.

BACKGROUND: Patients with recurrent or locally advanced head and neck squamous cell carcinoma (HNSCC) typically have limited treatment options and poor prognosis. AIM: To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating HNSCC. METHODS: This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 days. Intensity-modulated radiation therapy with a conventional fraction was delivered 5 days per week. Objective response rate (ORR), disease control rate, and toxicity were observed as primary endpoints. Overall survival (OS) and progression free survival were recorded and analyzed as secondary endpoints. RESULTS: A total of 24 patients with HNSCC were enrolled. During the median 22.4-mo follow-up, both ORR and disease control rate were 100%. The one-year OS was 75%, and one-year progression-free survival (PFS) was 66.7% (median PFS was 15.1 mo). Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients, and patients who achieved complete response had better survival than those in the PR group (all P < 0.05). The most common grade 1-4 (100%) or grade 3-4 toxicities (75%) were hematological, and the most common grade 3-4 non-hematological toxicity was mucositis in 17 (71%) patients. CONCLUSION: Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable tolerability. Considering the high adverse event rate, the optimized dose and schedule must be further explored.

Clinical and laboratory features of childhood-onset primary Sjögren's syndrome: A retrospective study from China.

Introduction: The initial presentations of childhood-onset primary Sjögren's syndrome (C-pSS) vary, making diagnosis challenging. We aimed to improve the diagnosis and evaluation of C-pSS by summarizing its clinical and laboratory features. Methods: A total of 49 patients with C-pSS between July 2015 and August 2022 in the Department of Rheumatology and Immunology of Shanghai Children's Medical Centre were enrolled in this study. Their clinical manifestations and laboratory examinations of these patients were compared based on the presence or absence of thrombocytopenia and parotitis and whether the immunological markers, including anti-nuclear antibodies (ANA), rheumatoid factor (RF), anti-Ro52/SSA antibodies (anti-SSA/Ro52), anti-Ro60/SSA antibodies (anti-SSA/Ro60), and anti-Ro/SSB antibodies (anti-SSB), were positive. Results: The mean age at C-pSS diagnosis was 10.34 ± 3.45 years, and the ratio of boys to girls was 1:6. In the thrombocytopenia group, parotitis (P = 0.044), organ involvement except for hematology (P = 0.002), positive anti-SSB (P = 0.004), and positive RF (P = 0.001) were less frequently observed. Complement C4 (P = 0.038) and white blood cells (P = 0.002) levels decreased and increased significantly, respectively. Anti-SSB (P = 0.010) and RF (P = 0.004) positivity were independent potential protective factors against thrombocytopenia in patients with C-pSS. In the parotitis group, higher ANA titers (P = 0.027), higher focus scores on labial gland biopsy (P = 0.024), and positive RF (P = 0.001), anti-SSA/Ro60 (P = 0.003), and anti-SSB (P = 0.001) were observed more frequently. Furthermore, positive anti-SSB (P = 0.012) and positive RF (P = 0.028) were independent risk factors for parotitis in patients with C-pSS. The hemoglobin level was significantly lower in patients with positive anti-SSA/Ro52 and positive anti-SSA/Ro60 results (P = 0.022 and P = 0.029, respectively), while immunoglobulin G level was significantly higher in patients in the same group (P = 0.048 and P = 0.007, respectively). Conclusions: Positive anti-SSB and positive RF values may be independent potential protective factors of thrombocytopenia in patients with C-pSS. In contrast, positive anti-SSB and positive RF were independent risk factors of parotitis in patients with C-pSS. More studies are needed to reveal the diagnostic role and pathogenic mechanism of immunological markers in C-pSS.

Chlorin e6-Biotin Conjugates for Tumor-Targeting Photodynamic Therapy.

To improve the tumor-targeting efficacy of photodynamic therapy, biotin was conjugated with chlorin e6 to develop a new tumor-targeting photosensitizer, Ce6-biotin. The Ce6-biotin had good water solubility and low aggregation. The singlet-oxygen generation rate of Ce6-biotin was slightly increased compared to Ce6. Flow cytometry and confocal laser scanning microscopy results confirmed Ce6-biotin had higher binding affinity toward biotin-receptor-positive HeLa human cervical carcinoma cells than its precursor, Ce6. Due to the BR-targeting ability of Ce6-biotin, it exhibited stronger cytotoxicity to HeLa cells upon laser irradiation. The IC50 against HeLa cells of Ce6-biotin and Ce6 were 1.28 µM and 2.31 µM, respectively. Furthermore, both Ce6-biotin and Ce6 showed minimal dark toxicity. The selectively enhanced therapeutic efficacy and low dark toxicity suggest that Ce6-biotin is a promising PS for BR-positive-tumor-targeting photodynamic therapy.

Construction and verification of prognostic nomogram for early-onset esophageal cancer.

This study aimed to build up nomogram models to evaluate overall survival (OS) and cancer-specific survival (CSS) in early-onset esophageal cancer (EOEC). Patients diagnosed with esophageal cancer (EC) from 2004 to 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Clinicopathological characteristics of younger versus older patients were compared, and survival analysis was performed in both groups. Independent related factors influencing the prognosis of EOEC were identified by univariate and multivariate Cox analysis, which were incorporated to construct a nomogram. The predictive capability of the nomogram was estimated by the concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). A total of 534 younger and 17,243 older patients were available from the SEER database. Younger patients were randomly segmented into a training set (n = 266) and a validation set (n = 268). In terms of the training set, the C-index of the OS nomogram was 0.740 (95% CI: 0.707-0.773), and that of the CSS nomogram was 0.752 (95% CI: 0.719-0.785). In view of the validation set, the C-index of OS and CSS were 0.706 (95% CI: 0.671-0.741) and 0.723 (95% CI: 0.690-0.756), respectively. Calibration curves demonstrated the consistent degree of fit between actual and predicted values in nomogram models. From the perspective of DCA, the nomogram models were more beneficial than the tumor-node-metastasis (TNM) and the SEER stage for EOEC. In brief, the nomogram model can be considered as an individualized quantitative tool to predict the prognosis of EOEC patients to assist clinicians in making treatment decisions.

A Radiomics Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Pancreatic Ductal Adenocarcinoma.

PURPOSE: To construct and verify a CT-based multidimensional nomogram for the evaluation of lymph node (LN) status in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We retrospectively assessed data from 172 patients with clinicopathologically confirmed PDAC surgically resected between February 2014 and November 2016. Patients were assigned to either a training cohort (n = 121) or a validation cohort (n = 51). We acquired radiomics features from the preoperative venous phase (VP) CT images. The maximum relevance-minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) methods were used to select the optimal features. We used multivariable logistic regression to construct a combined radiomics model for visualization in the form of a nomogram. Performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve approach, calibration testing, and analysis of clinical usefulness. RESULTS: A Rad score consisting of 10 LN status-related radiomics features was found to be significantly associated with the actual LN status (P < 0.01). A nomogram that consisted of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status performed well in terms of predictive power in the training cohort (area under the curve, 0.92), and this was confirmed in the validation cohort (area under the curve, 0.95). The nomogram also performed well in the calibration test and decision curve analysis, demonstrating its potential clinical value. CONCLUSION: A multidimensional radiomics nomogram consisting of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status may contribute to the non-invasive evaluation of LN status in PDAC patients.

Reversible antibiotic loading and pH-responsive release from polymer brushes on contact lenses for therapy and prevention of corneal infections.

Corneal infection is an important cause of corneal damage and vision loss. In this work, polyhydroxy antibiotics were grafted onto polymer brush-modified contact lenses through dynamic chemical bonds between polyphenolic hydroxyls and phenylboronic acid. Both in vitro and in vivo antibacterial tests demonstrated great promise in the prevention of bacterial keratitis, which could be attributed to the enhanced retention time and drug bioavailability.

Anti-HER2 Affibody-Conjugated Photosensitizer for Tumor Targeting Photodynamic Therapy.

Antibody-coupled photosensitive molecules can achieve an ideal tumor-specific photodynamic therapy (PDT) and show strong clinical application potential. However, some inherent disadvantages, such as long circulation half-life, poor permeation into solid tumors, and difficulty in obtaining uniform coupling products, present potential problems to clinical applications. In this study, we propose a novel design of targeting photosensitizers, based on a very small targeting protein (an affibody molecule) coupled with photosensitive compounds, to address these problems. In the synthesis, photosensitive pyropheophorbide-a (Pyro) is modified with a PEG linker (molecular weight of 727 Da) and then site specifically coupled to the anti-HER2 ZHER2:2891 affibody protein to provide a homogeneous protein-coupled photosensitizer via a convenient process. In vitro and in vivo experiments show that this molecule has an ideal selectivity for binding and photocytotoxicity against HER2-positive cells (more than 50-fold selectivity between HER2-high expression and HER2-low expression cells) and highly specific tumor accumulation; at a relatively low dose, it effectively eliminated HER2-high expression NCI-N87 tumors in a mouse model. It is worth noting that Pyro only has a moderate photodynamic activity; however, the affibody-coupled Pyro molecule (Pyro-Linker-ZHER2) still shows excellent tumor therapeutic function. The more ideal tumor permeability of small ligands may be helpful to enhance the drug concentration in the tumor site and the ability to penetrate deeply inside the tumor. Coupling photosensitive compounds with affibody proteins may provide a new way for targeting PDT of tumors.

Plasma Long Non-Coding RNA RP11-438N5.3 as a Novel Biomarker for Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer is one of the most common malignancies around the world. The lack of early diagnosis and effective treatment strategies contributes to the poor prognosis of patients with lung cancer. Recent studies have implied the role of long non-coding RNAs (lncRNAs) in oncogenesis. The purpose of our study was to identify specific lncRNAs which were correlated with non-small cell lung cancer (NSCLC) and their potential functions. MATERIALS AND METHODS: The global plasma lncRNA profiling was performed using LncPathTM Human Cancer Array, and 11 lncRNAs were then selected for quantitative reverse transcription PCR (qRT-PCR) validation in 138 plasma samples from 69 NSCLC patients and 69 healthy controls (HCs). A noteworthy lncRNA, RP11-438N5.3, the function of which was previously unknown, was further explored on the aspect of the correlation of its expression level with clinicopathological factors. RESULTS: The results revealed that plasma level of RP11-438N5.3 was significantly lower in NSCLCs than that in HCs (p <0.01). Receiver operating characteristic (ROC) analyses showed that the area under the ROC curve (AUC) for plasma RP11-438N5.3 was 0.814 (95% CI, 0.743-0.885; p<0.01). High expression of RP11-438N5.3 in plasma correlated with favorable prognosis for NSCLC patients (Hazard ratio = 2.827; 95% CI: 1.036 to 7.718; p = 0.024; Cox regression analysis). Moreover, we found that the plasma level of stromal interaction molecule 1 (STIM1) mRNA was remarkably higher in NSCLC compared with HC (p<0.01), and the AUC for STIM1 was 0.753 (95% CI, 0.673-0.833; p<0.01), RP11-438N5.3 and STIM1 were inversely correlated with each other. CONCLUSION: Our results indicated that RP11-438N5.3 and STIM1 might provide a new strategy for NSCLC diagnosis. Furthermore, increased circulating RP11-438N5.3 level holds great potential in indicating a beneficial prognosis in NSCLC patients.