Accuracy of the modified tooth-supported 3D printing surgical guides based on CT, CBCT, and intraoral scanning in maxillofacial region: A comparison study.

BACKGROUND: Tooth-supported surgical guides have demonstrated superior accuracy compared with bone-supported guides. This study aimed to modify the fabrication of tooth-supported guides for compatibility with tumor resection procedures and investigate their accuracy. METHODS: Patients with tumors who underwent osteotomy with the assistance of modified tooth- or bone-supported surgical guides were included. Virtual surgical planning (VSP) was employed to align three dimensional (3D) models extracted from intraoperative computed tomography (CT) images. The distances and angular deviations between the actual osteotomy plane and preoperative plane were recorded. A comparative analysis of osteotomy discrepancies between tooth-supported and bone-supported guides, as well as among tooth-supported guides based on CT, cone-beam CT (CBCT), or intraoral scanner (IOS) was conducted. The factors influencing the precision of the guides were analyzed. RESULTS: Sixty patients with 81 resection planes were included in this study. In the tooth-supported group, the mean deviations in the osteotomy plane and angle were 1.39 mm and 4.30°, respectively, whereas those of the bone-supported group were 2.16 mm and 4.95°. In the tooth-supported isotype guide groups, the mean deviations of the osteotomy plane were 1.39 mm, 1.47 mm, 1.23 mm across CT, CBCT, and IOS, respectively. The accuracy of the modified tooth-supported guides remained consistent regardless of number and position of the teeth supporting the guide and location of the osteotomy lines. CONCLUSIONS: The findings indicate that the modified tooth-supported surgical guides demonstrated high accuracy in the maxillofacial region, contributing to a reduction in the amount of surgically detached soft tissue.

METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.

The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.

Sole brachytherapy for inoperable, recurrent, and irradiated salivary gland cancer.

BACKGROUND AND PURPOSE: Salivary gland cancers (SGCs) are hard to treat when inoperable, and sole brachytherapy appears to be a promising therapeutic strategy. This study aimed to evaluate the effectiveness, safety, and capability of pain palliation using sole brachytherapy for inoperable, recurrent, and irradiated SGCs. MATERIALS AND METHODS: Patients with inoperable SGCs treated using sole brachytherapy at Peking University School and Hospital of Stomatology were retrospectively included. Patients were divided into primary and recurrent groups and irradiated and non-irradiated groups. Local control (LC), overall survival (OS), radiation-relevant toxicities, and Visual Analogue Scale (VAS) score for pain, were recorded and evaluated. RESULTS: A total of 176 patients from 2006 to 2020 were included. The 5-year LC rate was 48.6 %; for the primary, recurrent, non-irradiated and irradiated groups, the rates were 72.6 %, 39.5 %, 56.8 %, and 34.5 %, respectively. The 5-year OS rates was 52.6 %; for the primary, recurrent, non-irradiated, and irradiated groups, the rates were 62.9 %, 48.6 %, 58.9 %, and 42.3 %, respectively. The mean ± standard deviation of posttreatment VAS score of pain was 2.154 ± 2.989, which was significantly decreased from the score of 6.923 ± 2.280 prior to brachytherapy. Skin hyperpigmentation, mucositis, and dysphagia were the most frequently reported adverse events. CONCLUSIONS: Brachytherapy as a sole modality, was retrospectively proven effective and safe in the management of inoperable SGCs and was beneficial in multiple irradiation and pain control.

TRIM26 restricts Epstein-Barr virus infection in nasopharyngeal epithelial cells through K48-linked ubiquitination of HSP-90ß.

The tripartite interaction motif (TRIM) family of proteins is known for their antiviral activity through different mechanisms, such as interfering with viral components, regulating immune responses, and participating in autophagy-mediated defense pathways. In this study, we investigated the role of tripartite interaction motif 26 (TRIM26), which is encoded by a major histocompatibility complex (MHC) gene, in regulating Epstein-Barr virus (EBV) infection of nasopharyngeal epithelial cells. We found that TRIM26 expression was induced upon EBV infection and that it indirectly targeted EphA2, a crucial epithelial receptor for EBV entry. Our results showed that TRIM26 interacted with heat shock protein 90-beta (HSP-90ß) and promoted its polyubiquitination, which led to its degradation via the proteasome pathway. This, in turn, affected EphA2 integrity and suppressed EBV infection. These findings suggest that TRIM26 could be a valuable target for developing therapeutic interventions against EBV infection and its associated pathogenesis.

Label-free detection of vitamin B by two-step enhanced Raman technique using dynamic borohydride-reduced silver nanoparticles.

A creatively designed novel two-step enhancement technique is presented in which B vitamin molecules are dynamically adsorbed onto the surface of silver nanoparticles by sodium borohydride, followed by local plasmon resonance in the presence of cations (calcium ions), ultimately achieving synergistic chemical and physical enhancement on the same molecule and constructing a "surface hot spots" two-step enhancement platform for vitamin detection. The Raman signal of the promoted vitamin molecule is enhanced by nine orders of magnitude. In a subsequent study it was observed that the vitamin B2 molecules were in a near-vertical image on the surface of the silver nanoparticles, which may also contribute to the Raman signal enhancement. Combined with deep learning techniques, the method has been successfully applied to the detection of B vitamins in body fluids. As an accurate, rapid, reproducible, non-invasive, and versatile assay platform, it holds great promise for the intelligent identification of trace B molecules in food, pharmaceuticals, and the human body.

EBV-Associated Hub Genes as Potential Biomarkers for Predicting the Prognosis of Nasopharyngeal Carcinoma.

This study aimed to develop a model using Epstein-Barr virus (EBV)-associated hub genes in order to predict the prognosis of nasopharyngeal carcinoma (NPC). Differential expression analysis, univariate regression analysis, and machine learning were performed in three microarray datasets (GSE2371, GSE12452, and GSE102349) collected from the GEO database. Three hundred and sixty-six EBV-DEGs were identified, 25 of which were found to be significantly associated with NPC prognosis. These 25 genes were used to classify NPC into two subtypes, and six genes (C16orf54, CD27, CD53, CRIP1, RARRES3, and TBC1D10C) were found to be hub genes in NPC related to immune infiltration and cell cycle regulation. It was shown that these genes could be used to predict the prognosis of NPC, with functions related to tumor proliferation and immune infiltration, making them potential therapeutic targets. The findings of this study could aid in the development of screening and prognostic methods for NPC based on EBV-related features.

Advancing therapeutic strategies for Epstein-Barr virus-associated malignancies through lytic reactivation.

Epstein-Barr virus (EBV) is a widespread human herpes virus associated with lymphomas and epithelial cell cancers. It establishes two separate infection phases, latent and lytic, in the host. Upon infection of a new host cell, the virus activates several pathways, to induce the expression of lytic EBV antigens and the production of infectious virus particles. Although the carcinogenic role of latent EBV infection has been established, recent research suggests that lytic reactivation also plays a significant role in carcinogenesis. In this review, we summarize the mechanism of EBV reactivation and recent findings about the role of viral lytic antigens in tumor formation. In addition, we discuss the treatment of EBV-associated tumors with lytic activators and the targets that may be therapeutically effective in the future.

Long-term result of 125 I seed brachytherapy for pediatric desmoid tumor in the head and neck.

BACKGROUND: Desmoid tumor (DT) is rare and challenging, often affects the head and neck (HN) region in children, and its appropriate treatments are under-discussed. This study aimed to retrospectively evaluate the long-term effectiveness and safety of 125 I seed brachytherapy for pediatric DT in HN. PROCEDURE: Seven pediatric patients with a median age of three years who suffered from DT in HN treated with 125 I brachytherapy from January 2008 to June 2018 were included. Among these, five underwent sole brachytherapy and the others combined with surgery under prescription doses ranging from 10,000 to 12,000 cGy. The rate of local control (LC), complete response (CR), and partial response (PR) was calculated after evaluation by radiological and pathological means. Radiation-associated toxicities were also evaluated. RESULTS: The LC rate was 7/7 during the follow-up time ranging from 43 to 135 months and with a mean of 57 months. No recurrent lesion was found in the patients receiving surgery combined with brachytherapy. In patients treated with sole brachytherapy, the radiological PR rate and CR rate were 4/5 and 1/5, respectively. In those reaching radiological PR, 3/4 were pathological CR. Slight acute radiation-associated toxicities were observed in all patients, and no late or severe acute toxicity was observed. CONCLUSION: 125 I brachytherapy is effective and safe in the management of pediatric DT in HN as the sole modality or combined with surgery in the long term.

FOXD1-dependent RalA-ANXA2-Src complex promotes CTC formation in breast cancer.

BACKGROUND: Early metastasis is a key factor contributing to poor breast cancer (BC) prognosis. Circulating tumor cells (CTCs) are regarded as the precursor cells of metastasis, which are ultimately responsible for the main cause of death in BC. However, to date molecular mechanisms underlying CTC formation in BC have been insufficiently defined. METHODS: RNA-seq was carried out in primary tissues from early-stage BC patients (with CTCs≥5 and CTCs = 0, respectively) and the validation study was conducted in untreated 80 BC patients. Multiple in vitro and in vivo models were used in functional studies. Luciferase reporter, ChIP-seq, CUT&Tag-seq, and GST-pulldown, etc. were utilized in mechanistic studies. CTCs were counted by the CanPatrol™ CTC classification system or LiquidBiospy™ microfluidic chips. ERK1/2 inhibitor SCH772984 was applied to in vivo treatment. RESULTS: Highly expressed FOXD1 of primary BC tissues was observed to be significantly associated with increased CTCs in BC patients, particularly in early BC patients. Overexpressing FOXD1 enhanced the migration capability of BC cells, CTC formation and BC metastasis, via facilitating epithelial-mesenchymal transition of tumor cells. Mechanistically, FOXD1 was discovered to induce RalA expression by directly bound to RalA promotor. Then, RalA formed a complex with ANXA2 and Src, promoting the interaction between ANXA2 and Src, thus increasing the phosphorylation (Tyr23) of ANXA2. Inhibiting RalA-GTP form attenuated the interaction between ANXA2 and Src. This cascade culminated in the activation of ERK1/2 signal that enhanced metastatic ability of BC cells. In addition, in vivo treatment with SCH772984, a specific inhibitor of ERK1/2, was used to dramatically inhibit the CTC formation and BC metastasis. CONCLUSION: Here, we report a FOXD1-dependent RalA-ANXA2-Src complex that promotes CTC formation via activating ERK1/2 signal in BC. FOXD1 may serve as a prognostic factor in evaluation of BC metastasis risks. This signaling cascade is druggable and effective for overcoming CTC formation from the early stages of BC.

Clinical application and accuracy assessment of imaging-based surgical navigation guided 125I interstitial brachytherapy in deep head and neck regions.

Brachytherapy has the advantages of being minimally invasive and highly conformal, and it achieves good results in head and neck tumors. To precisely implant the radioactive seeds according to the preplan in deep head and neck regions, the surgical navigation is applied. This study aims to explore the clinical application and accuracy of imaging-based surgical navigation-guided 125I interstitial brachytherapy in terms of seed position. We included 41 patients with tumors in deep head and neck regions. The brachytherapy treatment plan was designed, and the preplanned data were transferred to the navigation system. Needle implantation and seed delivery were performed under surgical navigation system guidance with or without the combination of individual template. The treatment accuracy was evaluated by comparing seed cluster locations between the preoperative treatment plan and the postoperative treatment outcome. A total of 2879 seeds were delivered. The range, mean and median distances between the geometric centers of the preoperative seed point clusters and the postoperative seed point clusters were 0.8-10.5 mm, 4.5 ± 2.3 mm and 4.1 mm, respectively. The differences between preoperative and postoperative volumes of the minimum bounding box of seed point clusters were nonsignificant. In conclusion, the imaging-based surgical navigation system is a promising clinical tool to provide the preplanned data for interstitial brachytherapy intraoperatively, and it is feasible and accurate for the real-time guidance of needle implantation and seed delivery in deep head and neck regions.

Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis.

Increased vascular permeability facilitates metastasis. Cancer-secreted exosomes are emerging mediators of cancer-host crosstalk. Epstein-Barr virus (EBV), identified as the first human tumor-associated virus, plays a crucial role in metastatic tumors, especially in nasopharyngeal carcinoma (NPC). To date, whether and how exosomes from EBV-infected NPC cells affect vascular permeability remains unclear. Here, we show that exosomes from EBV-positive NPC cells, but not exosomes from EBV-negative NPC cells, destroy endothelial cell tight junction (TJ) proteins, which are natural barriers against metastasis, and promote endothelial-to-mesenchymal transition (EndMT) in endothelial cells. Proteomic analysis revealed that the level of HMGA2 protein was higher in exosomes derived from EBV-positive NPC cells compared with that in exosomes derived from EBV-negative NPC cells. Depletion of HMGA2 in exosomes derived from EBV-positive NPC cells attenuates endothelial cell dysfunction and tumor cell metastasis. In contrast, exosomes from HMGA2 overexpressing EBV-negative NPC cells promoted these processes. Furthermore, we showed that HMGA2 upregulates the expression of Snail, which contributes to TJ proteins reduction and EndMT in endothelial cells. Moreover, the level of HMGA2 in circulating exosomes is significantly higher in NPC patients with metastasis than in those without metastasis and healthy negative controls, and the level of HMGA2 in tumor cells is associated with TJ and EndMT protein expression in endothelial cells. Collectively, our findings suggest exosomal HMGA2 from EBV-positive NPC cells promotes tumor metastasis by targeting multiple endothelial TJ and promoting EndMT, which highlights secreted HMGA2 as a potential therapeutic target and a predictive marker for NPC metastasis.

Rationally Driven Drug Nonradiative Decay via a Label-Free Polyprodrug Strategy to Renew Tumor Cascade Photothermal-Chemotherapy.

Drugs are frequently used for only chemotherapy that ignores their photophysical properties that potentially endow them with other therapeutic potency. Additionally, current photothermal-chemotherapy replies on the codelivery of drugs and photothermal agents, but their spatiotemporal delivery and precise release is unsatisfactory. Herein, label-free doxorubicin (DOX) polyprodrug nanoparticles (DPNs) are formulated from disulfide bonds-tethered DOX polyprodrug amphiphiles (PDMA-b-PDOXM). Benefiting from boosted nonradiative decay of high-density DOX, significant fluorescence quenching and photothermal effects are observed for DPNs without common photothermal agents. Upon cellular uptake and laser irradiation, the heat can promote lysosomal escape of DPNs into reductive cytosol, whereupon free DOX is released to activate chemotherapy and fluorescence, achieving rational cascade photothermal-chemotherapy. The current label-free polyprodrug strategy can make full use of drugs; it provides an alternative insight to extend the therapeutic domain of drugs.

Epstein-Barr Virus Induces Lymphangiogenesis and Lympth Node Metastasis via Upregulation of VEGF-C in Nasopharyngeal Carcinoma.

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common Epstein-Barr virus (EBV)-associated head and neck malignancy. However, the effect of EBV on NPC lymph node (LN) metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF1a hyperactivity and subsequent VEGF-C transcriptional activation. In addition, administration of anti-VEGF-C antibody or HIF1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF1a, and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis. IMPLICATIONS: This research demonstrates that EBV induces lymphangiogenesis in NPC by regulating PHLPP1/p-AKT/HIF1a/VEGF-C, providing a new therapeutic target for NPC with lymphatic metastasis.

Fast Broad-Spectrum Staining and Photodynamic Inhibition of Pathogenic Microorganisms by a Water-Soluble Aggregation-Induced Emission Photosensitizer.

Pathogenic microorganisms pose great challenges to public health, which is constantly urgent to develop extra strategies for the fast staining and efficient treatments. In addition, once bacteria form stubborn biofilm, extracellular polymeric substance (EPS) within biofilm can act as protective barriers to prevent external damage and inward diffusion of traditional antibiotics, which makes it frequently develop drug-resistant ones and even hard to treat. Therefore, it is imperative to develop more efficient methods for the imaging/detection and efficient inhibition of pathogenic microorganisms. Here, a water-soluble aggregation-induced emission (AIE)-active photosensitizer TPA-PyOH was employed for fast imaging and photodynamic treatment of several typical pathogens, such as S. aureus, methicillin-resistant Staphylococcus aureus, L. monocytogenes, C. albicans, and E. coli. TPA-PyOH was non-fluorescent in water, upon incubation with pathogen, positively charged TPA-PyOH rapidly adhered to pathogenic membrane, thus the molecular motion of TPA-PyOH was restricted to exhibit AIE-active fluorescence for turn-on imaging with minimal background. Upon further white light irradiation, efficient reactive oxygen species (ROS) was in-situ generated to damage the membrane and inhibit the pathogen eventually. Furthermore, S. aureus biofilm could be suppressed in vitro. Thus, water-soluble TPA-PyOH was a potent AIE-active photosensitizer for fast fluorescent imaging with minimal background and photodynamic inhibition of pathogenic microorganisms.

Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma.

Elimination of the posttraumatic inflammatory response and recovery of homeostasis are crucial for the positive prognosis of trauma patients. Myeloid-derived suppressor cells (MDSCs) are known to play a regulatory role in the posttraumatic immune response in mice, but their induction source and involved potential mechanism are poorly understood. Here, we report that polymorphonuclear MDSCs (PMN-MDSCs) are activated after trauma and are closely associated with the progression of the posttraumatic inflammatory response. In humans, lectin-type oxidized LDL receptor 1 (LOX1) was used to specifically characterize LOX1+ PMN-MDSCs. Trauma patients showed high intracellular reactive oxygen species (ROS) production, as well as activation of LOX1+ PMN-MDSCs. These MDSCs contribute to the anti-inflammatory immune response by regulating the Treg/Th17 and Th2/Th1 balances after trauma, increasing the levels of anti-inflammatory factors, and decreasing the levels of proinflammatory factors. The number of LOX1+ PMN-MDSCs was positively correlated with the positive clinical prognosis of trauma patients with infection. Activation of LOX1+ PMN-MDSCs is mediated by NF-κB signal, and TGF-ß1 may be as an important inducer for LOX1+ PMN-MDSCs in the posttraumatic cytokine environment. In a pseudofracture trauma mouse model, we also observed the activation of PMN-MDSCs, accompanying high levels of intracellular ROS production, NF-κB phosphorylation, and changes in the inflammatory environment, in particularly by regulating the Treg/Th17 and Th2/Th1 balance. And more significantly, posttraumatic inflammation was alleviated in mice after transferring trauma-derived PMN-MDSCs, but aggravated after injecting with Gr1 agonistic antibody. These findings provide evidence for the specific role of PMN-MDSCs in the regulation of posttraumatic inflammation.

Nanoparticles as an effective drug delivery system in COVID-19.

BACKGROUND: The global healthcare sector has been dealing with a situation known as a novel severe acute respiratory syndrome (SARS-CoV-2) since the end of 2019. Covid-19 is an acronym for Covid-19 (Coronavirus Disease- 2019). It causes a respiratory infection that includes cold, sneezing and coughing, and pneumonia. In the case of an animal, it causes diarrhea and upper respiratory diseases. Covid-19 transmitted human to human via airborne droplets. First Covid-19 emerged in Wuhan market China and it spread rapidly throughout the World. As we know nanoparticles are a novel drug delivery system. They have various advantageous effects like increasing the efficacy of the drug, safety, etc. In this review, we study about the nanoparticles and summarize how it is effective during drug delivery system in Covid-19. Chitosan is a much focused biopolymeric nanoparticle. It delivers drugs to the specific target site. In a recent health crisis, chitosan nanoparticles are one of the ways to release drugs of Covid-19, and specifically in the lungs of the affected patients. We studied and extracted our data from various research papers, review papers, and some other articles. OBJECTIVE: The main goal is to study the nanoparticles and their future aspects which is an effective drug delivery system in Covid-19. METHODS: The bibliographic search was done through a systematic search. The terms "Nanoparticles", "Covid-19 ", "Drug delivery" etc. were used to search the databases/search engines like "Google Scholar", "NCBI", "PubMed", "Science Direct" etc. These databases and search engines used here perform the limited criteria of search to conduct a systematic literature survey for the study and report writing. All the text from the articles and research papers were studied and analyzed. The various articles and research papers were used in writing this report and all of which are mentioned in the reference section of this report. CONCLUSION: Our current studies reveal that nanoparticles may prove very helpful in the delivery of drugs for Covid-19 treatment. Many cases showed that patients, where drugs are delivered with the help of nanoparticles, produced very few side effects.

Potential of nanoparticles encapsulated drugs for possible inhibition of the antimicrobial resistance development.

The immune system is a dynamic network of cells and cytokines are the major mediators of immune responses which combat pathogens. Based on the cytokine production, effector T cells differentiate into subsets known as Th1, Th2, Th17, or Treg. This system serves as a barrier to intracellular pathogens, bacterial infections and stimulates the production of reactive oxygen species (ROS), reactive nitrogen intermediates, and nitric oxide, which diffuses across membranes and engulfs intracellular pathogens. Oxidative stress occurs when ROS, reactive nitrogen species (RNS) production, and antioxidant defences become imbalanced. Oxidative stress generated by infected cells produces a substantial amount of free radicals which enables the killing of intracellular pathogens. Intracellular pathogens are exposed to endogenous ROS as part of normal aerobic respiration, also exogenous ROS and RNS are generated by the host immune system in response to infection. Nanoparticles which are designed for drug delivery are capable of trapping the desired drug in the particles which protect the drug from enzymatic degradation in a biological system. The subcellular size of nanoparticles enables higher intracellular uptake of the drug which results in the reduction of the concentration of free drugs reducing their toxic effect. Research on the modulation of immune response and oxidative stress using nanoparticles used to encapsulate drugs has yet to be explored fully. In this review, we illustrate the immune activation and generation of oxidative stress properties which are mediated by nanoparticle encapsulated drug delivery systems which can make the therapy more effective in case of diseases caused by intracellular pathogens.

[Therapeutic Effect of Imatinib Made in Real World to Newly Diagnosed Chronic Myeloid Leukemia].

OBJECTIVE: To evaluate the clinical efficacy and safety of domestic imatinib (made in China) in patients with newly diagnosed chronic myeloid leukemia chronic phase(CML-CP). METHODS: Fifty-seven newly diagnosed CML-CP patients who did not receive any other anti-CML treatment were treated by domestic imatinib 400 mg once a day. The hematological, cytogenetic and molecular reactions and safety were observed and evaluated after 3, 6 and 12 months of treatment. RESULTS: Fifty-six patients were treated for ≥3 and 6 months, among which 50 patients were treated for ≥12 months. After 3 months of treatment, 49 patients underwent hematological examination, 47 patients (95.9%) achieved complete hematological response (CHR), 49 patients underwent cytogenetic examination, 39 patients (79.6%) achieved major cytogenetic response (MCyR), and 12 patients (24.5%) achieved complete cytogenetic response (CCyR). 49 patients underwent the level of BCR-ABL test, including 41 patients (83.7%) with BCR-ABLIS≤10%, and 5 patients (10.2%) with major molecular response (MMR: BCR-ABLIS ≤ 0.1%). After 6 months of treatment, 49 patients underwent hematological examination, and 49 patients (100%) all achieved CHR. 49 patients underwent cytogenetic examined, of which 41 cases (83.7%) obtained MCyR and 31 cases (65.3%) obtained CCyR. 49 patients underwent the level of BCR-ABL test, among which 33 patients (67.4%) showed BCR-ABLIS≤1%, and 15 patients(30.6%) reached MMR. After 12 months of treatment, 45 patients underwent hematological examination, and all the patients (100%) got CHR. 45 patients underwent cytogenetic examined, of which 41 cases (91.1%) obtained MCyR and 35 cases (77.8%) obtained CCyR. 45 cases were tested for BCR-ABL level, and 24 cases (55.3%) reached MMR. The incidence of grade Ⅲ leukopenia, thrombocytopenia and anemia were 14.0%, 8.7% and 10.5%, respectively. Non-hematological adverse reactions were edema (64.9%), nausea (50.9%), vomiting (35.1%), rash (24.5%), fever (15.8%), bone and joint muscle pain (38.6%), diarrhea(17.6%) and liver function damage (3.5%). There were no grade IV hematological and non-hematological adverse reactions. CONCLUSION: In the real world, Domestics imatinib mesylate is effective and safe in the treatment of newly diagnosed CML-CP patients, but long-term follow-up data are still necessary to verify its long-term efficacy.

Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer.

Gene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.