Near-infrared light triggered upconversion nanocomposites with multifunction of enhanced antimicrobial photodynamic therapy and gas therapy for inflammation regulation.

Antibacterial photodynamic therapy (aPDT) is highly effective in killing bacteria, while the problem of hypoxia and limited light penetration in deep tissue has not been properly solved. In addition, few aPDT works take into account the regulation of inflammation, which is an important regulatory process after antimicrobial therapy and the final purpose of treatment. In this work, to address the above isssues, we have designed a multi-functional composite UCNPs-Ce6-Mn(CO)5Br@Silane (referred to as UCM@Si), which consists of several key components: Up-conversion nanoparticles (UCNPs: NaErF4:Tm3+@NaYF4:Yb3+), Chlorin e6 (Ce6) and Manganese pentacarbonyl bromide (Mn(CO)5Br). When exposed to near-infrared (NIR) light (980 nm), the UCNPs can emit strong red light at 655 nm which further trigger the aPDT of Ce6. The generated reactive oxygen (ROS) subsequently break the metal carbonyl bond of Mn(CO)5Br, leading to the production of carbon monoxide (CO) molecules as well as manganese ions (Mn2+), which further decomposes hydrogen peroxide (H2O2) in the microenvironment to oxygen (O2). Therefore, this simple nanocomposite not only provides substantial self-oxygen replenishment for enhanced aPDT, but also facilitates effective inflammation regulation via CO across a wide range of deep infections. This approach leverages the unique properties of these materials to combat bacterial infections by simultaneously killing bacteria, regulating inflammation, and enhancing the oxygen levels in the affected microenvironment. This O2 and CO gas based aPDT treatment system offers a promising approach to comprehensively address microbial-induced infectious diseases, particularly deep infections, holding the potential clinical applications.

Pedigree genome data of an early-matured Geng/japonica glutinous rice mega variety Longgeng 57.

By using PacBio HiFi technology, we produced over 700 Gb of long-read sequencing (LRS) raw data; and by using Illumina paired-end whole-genome shotgun (WGS) sequencing technology, we generated more than 70 Gb of short-read sequencing (SRS) data. With LRS data, we assembled one genome and then generate a set of annotation data for an early-matured Geng/japonica glutinous rice mega variety genome, Longgeng 57 (LG57), which carries multiple elite traits including good grain quality and wide adaptability. Together with the SRS data from three parents of LG57, pedigree genome variations were called for three representative types of genes. These data sets can be used for deep variation mining, aid in the discovery of new insights into genome structure, function, and evolution, and help to provide essential support to biological research in general.

Identification of reliable QTLs and designed QTL breeding for grain shape and milling quality in the reciprocal introgression lines in rice.

Milling quality (MQ) and grain shape (GS) of rice (Oryza sativa L.) are correlated traits, both determine farmers' final profit. More than one population under multiple environments may provide valuable information for breeding selection on these MQ-GS correlations. However, suitable analytical methods for reciprocal introgression lines with linkage map for this kind of correlation remains unclear. In this study, our major tasks were (1) to provide a set of reciprocal introgression lines (composed of two BC2RIL populations) suitable for mapping by linkage mapping using markers/bins with physical positions; (2) to test the mapping effects of different methods by using MQ-GS correlation dissection as sample case; (3) to perform genetic and breeding simulation on pyramiding favorite alleles of QTLs for representative MQ-GS traits. Finally, with four analysis methods and data collected under five environments, we identified about 28.4 loci on average for MQ-GS traits. Notably, 52.3% of these loci were commonly detected by different methods and eight loci were novel. There were also nine regions harboring loci for different MQ-GS traits which may be underlying the MQ-GS correlations. Background independent (BI) loci were also found for each MQ and GS trait. All these information may provide useful resources for rice molecular breeding.

Aggressive local therapy for de novo metastatic breast cancer: Challenges and updates (Review).

Systemic therapy has been viewed as the mainstay for de novo metastatic breast cancer (dnMBC). However, as dnMBC is highly heterogeneous both biologically and clinically, and with ever-improving systemic strategies, it has been implied that the local therapy of the primary tumor (PT) may be beneficial for certain patients with dnMBC. However, the results from retrospective studies have been questioned due to their selection bias and retrospective nature. To the best of our knowledge, there are two published randomized clinical trials addressing this issue with conflicting conclusions: i) TATA study from India indicated no overall survival (OS) superiority with early local radiotherapy (LRT); and ii) MF07-01 indicated a 5-year OS rate improvement of 17% with upfront LRT. The updated results of a randomized phase III ECOG-ACRIN E2108 trial released in the 2020 American Society of Clinical Oncology (ASCO) meeting reported a negative survival effect of early LRT treatment in patients with dnMBC responding to initial systemic treatment, despite LRT significantly reducing the locoregional failure. Thus, a number of issues, such as the exact value of LRT, the optimal means of LRT (surgery and/or RT to the PT), the ideal timing of LRT and the population most likely to benefit from LRT, warrant further investigation. Herein, the related studies focusing on these aspects were comprehensively reviewed and a decision algorithm was proposed to select suitable patients with dnMBC for reasonable LRT. Generally, upfront systemic therapy is recommended. For good respondents and a subgroup of favorable profiles (young age, good general condition, low tumor burden, hormone receptor-positive and so on), radical LRT including PT surgery followed by RT and the resection of distant metastases is recommended. LRT should also be administered if the PT is still symptomatic. LRT may benefit patients with dnMBC due to the following reasons: Control of the PT decreases tumor burden, eliminates the source of dissemination, enhances the sensitivity to therapy and exerts positive immunomodulation. Therefore, the treatment paradigm for dnMBC may change from 'palliative LRT' into 'curative LRT' in a highly selected entity with careful evaluation.

The differences in learning motivation of college freshmen in Northwest China.

The study aimed to investigate the learning motivation of freshmen from a university in Northwest China, which can supply a reference for improving their learning quality and objectives. Data were collected from 800 freshmen of different majors with a learning motivation questionnaire. Differences in learning motivation between different majors, genders, regions, and students are studied. The results show that gender, seeking knowledge orientation, and material pursuit have significant effects on students' learning motivation. The gender had a significant impact on personal achievement and the only child or not had an obvious effect on material pursuit, while other factors had no obvious difference in gender, regional, and only child or not, while other factors on the gender, regional, and whether the one-child had no obvious difference. According to the results of the research, measures to improve learning motivation are proposed. Our research results provide a reference for improving learning attitude and the quality of universities.

Computational method using heterogeneous graph convolutional network model combined with reinforcement layer for MiRNA-disease association prediction.

BACKGROUND: A large number of evidences from biological experiments have confirmed that miRNAs play an important role in the progression and development of various human complex diseases. However, the traditional experiment methods are expensive and time-consuming. Therefore, it is a challenging task that how to develop more accurate and efficient methods for predicting potential associations between miRNA and disease. RESULTS: In the study, we developed a computational model that combined heterogeneous graph convolutional network with enhanced layer for miRNA-disease association prediction (HGCNELMDA). The major improvement of our method lies in through restarting the random walk optimized the original features of nodes and adding a reinforcement layer to the hidden layer of graph convolutional network retained similar information between nodes in the feature space. In addition, the proposed approach recalculated the influence of neighborhood nodes on target nodes by introducing the attention mechanism. The reliable performance of the HGCNELMDA was certified by the AUC of 93.47% in global leave-one-out cross-validation (LOOCV), and the average AUCs of 93.01% in fivefold cross-validation. Meanwhile, we compared the HGCNELMDA with the state­of­the­art methods. Comparative results indicated that o the HGCNELMDA is very promising and may provide a cost­effective alternative for miRNA-disease association prediction. Moreover, we applied HGCNELMDA to 3 different case studies to predict potential miRNAs related to lung cancer, prostate cancer, and pancreatic cancer. Results showed that 48, 50, and 50 of the top 50 predicted miRNAs were supported by experimental association evidence. Therefore, the HGCNELMDA is a reliable method for predicting disease-related miRNAs. CONCLUSIONS: The results of the HGCNELMDA method in the LOOCV (leave-one-out cross validation, LOOCV) and 5-cross validations were 93.47% and 93.01%, respectively. Compared with other typical methods, the performance of HGCNELMDA is higher. Three cases of lung cancer, prostate cancer, and pancreatic cancer were studied. Among the predicted top 50 candidate miRNAs, 48, 50, and 50 were verified in the biological database HDMMV2.0. Therefore; this further confirms the feasibility and effectiveness of our method. Therefore, this further confirms the feasibility and effectiveness of our method. To facilitate extensive studies for future disease-related miRNAs research, we developed a freely available web server called HGCNELMDA is available at http://124.221.62.44:8080/HGCNELMDA.jsp .

Successful treatment using targeted therapy, radiotherapy, and intrathecal chemotherapy in a patient with leptomeningeal metastasis with an epidermal growth factor receptor exon 20 insertion mutation: a case report.

Leptomeningeal metastasis (LM) is a disastrous complication in lung cancer. LM patients with oncogene-addicted non-small cell lung cancer (NSCLC) have a relatively better prognosis than those with the wild-type counterpart; however, overall post-LM survival is short. Additionally, the high heterogenicity of the LM entity creates a treatment challenge, and to date, no standard strategy has been established. This article describes a female lung adenocarcinoma patient with a resistant epidermal growth factor receptor (EGFR) exon20ins mutation who developed LM only 11 months after radical surgery IIIA (pT1bN2). Intrathecal chemotherapy (ITC), whole-brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) followed by Osimertinib was initiated. The cerebrospinal fluid (CSF) cytology turned negative. The first remission lasted 6 months, then bone metastases occurred, and the LM progressed. An Ommaya reservoir was implanted. ITC with pemetrexed and anlotinib was administered. A CSF next-generation sequencing (NGS) examination revealed EGFR exon20ins (p. A767_V769 dup 1.5%), which was different from that of the primary tumor (p. V769_D770 ins ASV 17.48%). The CSF cytology then turned negative again; however, the patient succumbed to the disease in December 2020. The patient's post-LM overall survival (OS) time was 13.5 months. This case is novel and of great value. Clinicians should pay special attention to populations at high risk of developing LM. Early detection followed by active intervention, including ITC, RT, and systemic treatment, will result in a better prognosis. The NGS of CSF is fundamental to understanding the genetic profiles of LM and providing effective and precise treatment.

The Relationship Between Perceived Stress, State-Trait Anxiety, and Sleep Quality Among University Graduates in China During the COVID-19 Pandemic.

The study aimed to investigate the relationship among perceived stress, state-trait anxiety, and sleep quality of graduates to provide a reference for improving their psychological status and attitude adjustment of job-searching during the COVID-19 pandemic. The research was conducted in a descriptive cross-sectional online survey between May 2020 and August 2020. The data were collected from 1,200 participants by using the personal information form prepared by the researchers in line with the literature, the Perceived Stress Scale, the State-Trait Anxiety Inventory, and the Pittsburgh Sleep Quality Index (PSQI). Among the surveyed participants, 47.67% were female, and 10.92% were medical students. The mean perceived stress, state anxiety, trait anxiety, and sleep quality were moderate and found as 31.4±6.69, 46.67±5.80, 49.45±5.54, and 5.94±2.47, respectively. The detection rates of state anxiety and trait anxiety were 48.63 and 49.50%, respectively. There was no significant difference in the detection rate of state anxiety and trait anxiety among different genders and majors (p >0.05). The detection rate of state anxiety and trait anxiety of rural family students was higher than that of urban family students (p <0.01). The score on the PSQI was positively associated with the scores on the perceived stress, state anxiety, and trait anxiety scales (p <0.001 for each model). Sleep quality was associated with increased perceived stress, state anxiety, and trait anxiety among graduates in China. Collectively, the study revealed the relationship between perceived stress, state-trait anxiety, and sleep quality among university graduates in China during the COVID-19 pandemic. Our results offer novel practical implications for all circles of the society to ensure students' health under the context of the COVID-19 epidemic.

EGFR-mutated stage IV non-small cell lung cancer: What is the role of radiotherapy combined with TKI?

Lung cancer is the leading cause of cancer-related death globally and poses a considerable threat to public health. Asia has the highest prevalence of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC). Despite the reasonable response and prolonged survival associated with EGFR-tyrosine kinase inhibitor (TKI) therapy, the acquisition of resistance to TKIs remains a major challenge. Additionally, patients with EGFR mutations are at a substantially higher risk of brain metastasis compared with those harboring wild-type EGFR. The role of radiotherapy (RT) in EGFR-mutated (EGFRm) stage IV NSCLC requires clarification, especially with the advent of next-generation TKIs, which are more potent and exhibit greater central nervous system activity. In particular, the feasible application of RT, including the timing, site, dose, fraction, and combination with TKI, merits further investigation. This review focuses on these key issues, and provides a flow diagram with proposed treatment options for metastatic EGFRm NSCLC, aiming to provide guidance for clinical practice.

Combined embedding model for MiRNA-disease association prediction.

BACKGROUND: Cumulative evidence from biological experiments has confirmed that miRNAs have significant roles to diagnose and treat complex diseases. However, traditional medical experiments have limitations in time-consuming and high cost so that they fail to find the unconfirmed miRNA and disease interactions. Thus, discovering potential miRNA-disease associations will make a contribution to the decrease of the pathogenesis of diseases and benefit disease therapy. Although, existing methods using different computational algorithms have favorable performances to search for the potential miRNA-disease interactions. We still need to do some work to improve experimental results. RESULTS: We present a novel combined embedding model to predict MiRNA-disease associations (CEMDA) in this article. The combined embedding information of miRNA and disease is composed of pair embedding and node embedding. Compared with the previous heterogeneous network methods that are merely node-centric to simply compute the similarity of miRNA and disease, our method fuses pair embedding to pay more attention to capturing the features behind the relative information, which models the fine-grained pairwise relationship better than the previous case when each node only has a single embedding. First, we construct the heterogeneous network from supported miRNA-disease pairs, disease semantic similarity and miRNA functional similarity. Given by the above heterogeneous network, we find all the associated context paths of each confirmed miRNA and disease. Meta-paths are linked by nodes and then input to the gate recurrent unit (GRU) to directly learn more accurate similarity measures between miRNA and disease. Here, the multi-head attention mechanism is used to weight the hidden state of each meta-path, and the similarity information transmission mechanism in a meta-path of miRNA and disease is obtained through multiple network layers. Second, pair embedding of miRNA and disease is fed to the multi-layer perceptron (MLP), which focuses on more important segments in pairwise relationship. Finally, we combine meta-path based node embedding and pair embedding with the cost function to learn and predict miRNA-disease association. The source code and data sets that verify the results of our research are shown at https://github.com/liubailong/CEMDA . CONCLUSIONS: The performance of CEMDA in the leave-one-out cross validation and fivefold cross validation are 93.16% and 92.03%, respectively. It denotes that compared with other methods, CEMDA accomplishes superior performance. Three cases with lung cancers, breast cancers, prostate cancers and pancreatic cancers show that 48,50,50 and 50 out of the top 50 miRNAs, which are confirmed in HDMM V2.0. Thus, this further identifies the feasibility and effectiveness of our method.

Giant Fungated Locally Advanced Breast Carcinoma Responded to Hypofractionated Radiotherapy Combined with Apatinib: A Case Report and Literature Review.

Locally advanced breast cancer (LABC) is frequently encountered in clinical practice. Primary systemic therapy is regarded as the cornerstone of LABC management to downstage the disease and enable surgery. However, multiple lines of systemic agents may fail to control tumor growth in a considerable number of patients, and few options remain available for such patients. Here, we present a case of triple-negative, right breast cancer that progressed aggressively despite 3 lines of standard chemotherapy. The patient suffered from severe skin ulceration, bleeding, pain, infection, and fungation. The small-molecular tyrosine kinase inhibitor (TKI) apatinib was initiated, which targets vascular endothelial growth factor receptor 2 (VEGFR2). The patient then underwent hypofractionated irradiation applied to the whole right breast at 40 Gy/8 f. The tumor responded dramatically to this combination, and a near-complete remission (CR) response was achieved 2 months after irradiation. Our case is novel and instructional and demonstrated the efficacy and safety of hypofractionated irradiation combined with antiangiogenesis for the treatment of intractable LABC, shedding light on this difficult situation. In the near future, large-scale clinical trials will be initiated to further explore this issue.

Unexpected massive bleeding caused by extensive maxillary osteonecrosis in a breast cancer patient: a case report.

Diphosphonate application is routinely recommended to treat bone metastasis (BM) in cancer patients. However, the severe side effects of diphosphonate, especially after long-term use, are often overlooked by clinicians. In this article, we describe a case in which a heavily-treated breast cancer patient, suffered from massive bleeding as a result of maxillary osteonecrosis by zoledronic acid (ZA) and apatinib. In October 2018, a 48-year-old Chinese female with breast cancer presented at our department with brain metastases. The patient had experienced progression multiple times and had received several lines of systemic interventions. ZA was administered monthly for a rather long period of 37 months. She also took 250 mg of apatinib, a small molecular tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor 2, daily for 11 days. However, massive bleeding from the oral and nasal cavity occurred that could not be alleviated by conventional means. Computed tomography revealed severe destruction and loss of the right maxillary bone and maxillary sinus wall. A pathological examination of the exfoliated bone tissue further confirmed that the patient was suffering from necrosis rather than metastasis. An emergency interventional embolization was performed, and the bleeding was stopped. In this case, maxillary osteonecrosis developed from the antiresorptive agents. Antiangiogenesis drugs should be avoided whenever possible. In clinical practice, the high risk of osteonecrosis needs to be carefully considered. Further, care needs to be taken to ensure osteonecrosis is not misdiagnosed as BM, especially in stage IV patients. Pathology is a prerequisite for the timely and correct diagnosis and management. Life-threatening toxicity such as massive bleeding, should be avoided to ensure that patients receive adequate antitumor treatments.

Bacillus amyloliquefaciens Rescues Glycyrrhizic Acid Loss Under Drought Stress in Glycyrrhiza uralensis by Activating the Jasmonic Acid Pathway.

Drought is a major factor limiting the production of the perennial medicinal plant Glycyrrhiza uralensis Fisch. (Fabaceae) in Northwest China. In this study, 1-year-old potted plants were inoculated with the strain Bacillus amyloliquefaciens FZB42, using a gradient of concentrations (CFU), to test for microbe-induced host tolerance to drought condition treatments in a greenhouse experiment. At the concentration of 108 CFU ml-1, FZB42 had significant growth-promoting effect on G. uralensis: the root biomass was 1.52, 0.84, 0.94, and 0.38 times that under normal watering and mild, moderate, and severe drought stress conditions, respectively. Under moderate drought, the positive impact of FZB42 on G. uralensis growth was most pronounced, with both developing axial and lateral roots strongly associated with indoleacetic acid (IAA) accumulation. An untargeted metabolomic analysis and physiological measurements of mature roots revealed that FZB42 improved the antioxidant system of G. uralensis through the accumulation of proline and sucrose, two osmotic adjustment solutes, and by promoting catalase (CAT) activity under moderate drought stress. Furthermore, significantly higher levels of total flavonoids, liquiritin, and glycyrrhizic acid (GA), the pharmacologically active substances of G. uralensis, were found in the roots of inoculated plants after FZB42 inoculation under all imposed drought conditions. The jasmonic acid (JA) content, which is closely related to plant defense responses and secondary metabolites' production, was greatly increased in roots after the bacterial inoculations, indicating that FZB42 activated the JA pathway. Taken together, our results demonstrate that inoculation with FZB42 alleviates the losses in production and pharmacological metabolites of G. uralensis caused by drought via the JA pathway's activation. These results provide a developed prospect of a microbial agent to improve the yield and quality of medical plants in arid and semi-arid regions.

Predicting MiRNA-disease associations by multiple meta-paths fusion graph embedding model.

BACKGROUND: Many studies prove that miRNAs have significant roles in diagnosing and treating complex human diseases. However, conventional biological experiments are too costly and time-consuming to identify unconfirmed miRNA-disease associations. Thus, computational models predicting unidentified miRNA-disease pairs in an efficient way are becoming promising research topics. Although existing methods have performed well to reveal unidentified miRNA-disease associations, more work is still needed to improve prediction performance. RESULTS: In this work, we present a novel multiple meta-paths fusion graph embedding model to predict unidentified miRNA-disease associations (M2GMDA). Our method takes full advantage of the complex structure and rich semantic information of miRNA-disease interactions in a self-learning way. First, a miRNA-disease heterogeneous network was derived from verified miRNA-disease pairs, miRNA similarity and disease similarity. All meta-path instances connecting miRNAs with diseases were extracted to describe intrinsic information about miRNA-disease interactions. Then, we developed a graph embedding model to predict miRNA-disease associations. The model is composed of linear transformations of miRNAs and diseases, the means encoder of a single meta-path instance, the attention-aware encoder of meta-path type and attention-aware multiple meta-path fusion. We innovatively integrated meta-path instances, meta-path based neighbours, intermediate nodes in meta-paths and more information to strengthen the prediction in our model. In particular, distinct contributions of different meta-path instances and meta-path types were combined with attention mechanisms. The data sets and source code that support the findings of this study are available at https://github.com/dangdangzhang/M2GMDA . CONCLUSIONS: M2GMDA achieved AUCs of 0.9323 and 0.9182 in global leave-one-out cross validation and fivefold cross validation with HDMM V2.0. The results showed that our method outperforms other prediction methods. Three kinds of case studies with lung neoplasms, breast neoplasms, prostate neoplasms, pancreatic neoplasms, lymphoma and colorectal neoplasms demonstrated that 47, 50, 49, 48, 50 and 50 out of the top 50 candidate miRNAs predicted by M2GMDA were validated by biological experiments. Therefore, it further confirms the prediction performance of our method.

Primary Pulmonary Diffuse Large B Cell Lymphoma Mimicking Metastasis: A Case Report and Literature Review.

Primary pulmonary diffuse large B cell lymphoma (PPDLBCL) is extremely rare, with fewer than 40 cases reported to date and a lack of systemic analysis. Herein, we present a case of PPDLBCL mimicking metastasis in a heavily treated patient with breast cancer. To our knowledge, this is the first reported case of PPDLBCL in a patient with breast cancer. A 66-year-old Chinese female diagnosed with breast cancer 7.5 years previously and multiple bone metastases 31 months later presented with a new-onset subpleural nodule in the inferior lobe of left lung detected by routine follow-up in November 2017. A 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography scan showed that the pulmonary nodule was hypermetabolic with a maximum standard uptake value of 14.9, consistent with lung metastasis in view of her history of breast cancer and multiple bone involvement. Surprisingly, pathologic investigation revealed primary lung DLBCL, staged IEA. Systemic chemotherapy with R-CDOP (rituximab, cyclophosphamide, vindesine, doxorubicin liposome, and prednisone) achieved complete remission with mild side effects. At the latest follow-up in August 2019, the patient had disease-free survival of 21 months. The findings from this case indicate that primary pulmonary lymphoma should be included in the differential diagnostic checklist of pulmonary occupancy, even in solid tumor patients treated with multiple modalities. When a newly developed lung nodule is identified in such patients, clinicians should not take for granted that it is lung metastasis. Pathology results are a prerequisite for making a correct diagnosis, choosing appropriate treatment, and improving patient prognosis.

Intramedullary spinal cord metastasis in malignancies: an institutional analysis and review.

Background: Intramedullary spinal cord metastases (ISCM) in malignancies is a devastating issue with limited research. This study aims to identify the clinical features, management, prognostic factors, and outcomes of this special entity. Methods: A retrospective review of 61 patients of ISCM diagnosed and treated in our institute from June 2010 to March 2018 was conducted (lost to follow-up: 3). Data were retrieved according to the items including age, gender, primary tumor, interval to the ISCM occurrence, ISCM segments, and other synchronous metastases. The interventions, response, prognostic factors, and outcomes of ISCM were systematically analyzed. Results: Lung cancer (67.21%) was the commonest ISCM source, followed by breast cancer (14.75%). In total, 9.84% of patients presented with ISCM initially. The mean span from the primaries to ISCM was 18.77 months (range=0-10 years). The thoracic segment was most commonly involved (77.05%), followed by cervical (39.34%), lumbar level (34.43%), and conus medullaris (6.56%). The management of ISCM was challenging, since 55.74% of individuals had a poor physical condition (PS=3-4) and 72.41% had widespread dissemination synchronously (≥2 organs). Radiotherapy (RT) attained an objective response rate (ORR) of 61.90% or 62.50% and a local control rate (LCR) of 90.48% or 87.50% for symptoms used alone or with other strategies, respectively. ISCM bears a dismal prognosis, with a median overall survival (OS) of 4 months. Patients with only one segment involved had an apparently better prognosis than those with 2-4 involved segments (median OS=7.0 vs 3.0 months) (P<0.01). The OS of patients treated was remarkably superior to those without any intervention (median OS=5.0 vs 2.0 months) (P<0.01). Conclusion: ISCM is a distinct entity needing more attention for high cancer incidence, prolonged survival, and lack of research. RT is the mainstay with satisfactory effect. Multiple spinal cord segments involvement and no treatment are poor prognostic factors of OS.

Lung cancer in young adults aged 35 years or younger: A full-scale analysis and review.

Objectives: Lung cancer in young adults is a distinct disease with particular socioeconomic implications. This study aimed to clarify the clinicopathological characteristics, best interventions, and outcomes of this distinctive entity. Methods: A retrospective review of patients with lung cancer was performed in our institute from January 2010 to June 2017. Young adults were defined as between 18 and 35 years old. Demographic, clinicopathological, therapeutic, and prognostic data were systematically analyzed. Results: From a total of 8734 patients, 120 (1.37%) were young adults, of which 82 with complete hospital records were included in this study. A high proportion had adenocarcinoma (45%) and late-stage disease (49.21% stage IV at diagnosis). Pleura (38.71%) were the most common metastatic site, followed by bone (35.48%) and lung (25.81%). The majority (68%) had single organ metastasis. Young patients had an increased frequency of gene mutations. Among the 18 patients for whom epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) status was determined, 10 had sensitive EGFR mutations while 5 had ALK rearrangement; only 3 patients were driver gene mutation-negative. The 1-year overall survival (OS) rate was 62.31% and the 3- and 5-year survival rates were both 53.31%; median OS was not achieved (range, 3-86 months). Male sex, negative or unknown gene mutation status, stage IV, and squamous or small cell lung cancer were associated with poor prognosis (OS) in early-onset lung cancer. Conclusions: Lung cancer in young adults is distinctive, with adenocarcinoma and stage IV at presentation being predominant characteristics. Gene mutation assessment should be mandatory in this subgroup due to the increased likelihood of positive driver gene alterations, as individualized targeted therapy may achieve superior outcomes.

Ionizing radiation-induced growth in soft agar is associated with miR-21 upregulation in wild-type and DNA double strand break repair deficient cells.

DNA double strand breaks (DSBs) are a severe threat to genome integrity and a potential cause of tumorigenesis, which is a multi-stage process and involves many factors including the mutation of oncogenes and tumor suppressors, some of which are transcribed microRNAs (miRNAs). Among more than 2000 known miRNAs, miR-21 is a unique onco-miRNA that is highly expressed in almost all types of human tumors and is associated with tumorigenesis through its multiple targets. However, it remains unclear whether there is any functional link between DSBs and miR-21 expression and, if so, does the link contribute to DSB-induced genomic instability/tumorigenesis. To address this question, we used DNA-PKcs-/- (deficient in non-homologous end-joining (NHEJ)) and Rad54-/- (deficient in homologous recombination repair (HRR)) mouse embryonic fibroblasts (MEFs) since NHEJ and HRR are the major pathways for DSB repair in mammalian cells. Our results indicate that levels of miR-21 are elevated in these DSB repair (DSBR) deficient cells, and ionizing radiation (IR) further increases these levels in both wild-type (WT) and DSBR-deficient cells. Interestingly, IR stimulated growth in soft agar and this effect was greatly reduced by blocking miR-21 expression in both WT and DSBR-deficient cells. Taken together, our results suggest that either IR or DSBR-deficient can lead to an upregulation of miR-21 levels and that miR-21 is associated with IR-induced cell growth in soft agar. These results may help our understanding of DSB-induced tumorigenesis and provide information that could facilitate the development of new strategies to prevent DSB-induced carcinogenesis.

A protein-mRNA feedback exists in miR-21-associated E-selectin expression.

PURPOSE: To study whether miR-21, an oncogene associated with lung tumorigenesis, affects immune response. MATERIAL AND METHODS: Cancer immune-related 786 mRNA expression was compared in lung tissue from wild-type and miR-21 knock-in mice using NanoString technology. The significantly changed genes were verified using real-time PCR. E-Selectin (Sele) was subsequently identified for further examination using immunohistochemistry (IHC) and Western blot in the same lung tissue. The mouse Sele 3'untranslated region (3'-UTR) was searched to identify a miR-21 matching sequence. The Sele level in miR-21 mimic transfected mouse lung bronchial epithelial (LBE) cells was examined. RESULTS: We unexpectedly found that the Sele mRNA level significantly increased but the protein level significantly decreased in the lung tissue of miR-21 knock-in mice compared to the mRNA/protein levels in the lung tissue of wild-type mice. The mouse Sele 3'-UTR contains the key sequence that can be targeted by miR-21. The Sele levels decreased in mouse LBE cells after miR-21 mimic transfection. CONCLUSION: Sele is a potential miR-21 target. The opposing Sele levels at mRNA and protein suggest a feedback-regulation from protein to mRNA. The feedback-regulation in miR-21-suppressed gene expression indicates that we should carefully evaluate any data from mRNA array since they may not reflect real protein expression status.

Good local tumor control but lethal hemorrhage after apatinib treatment for intractable squamous carcinoma of the floor of the mouth: a case report.

The treatment of repeatedly recurrent carcinoma of the floor of the mouth (FOM) is challenging. There is no standard strategy for such patients with poor physical condition after multiple lines of treatment. Angiogenesis is a key in tumor initiation, growth, and dissemination. Apatinib, a potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for the treatment of late-stage gastric or gastroesophageal junction adenocarcinoma that is resistant to at least two lines of chemotherapy. Its application in intractable FOM squamous carcinoma has never been described before. Herein, we present the case of a heavily treated patient with FOM squamous carcinoma undergoing a third local relapse in the right region of the neck and anterior cervical region. Oral apatinib was administered daily at a dose of 250 mg. There was clear and rapid efficacy that led to complete remission. However, giant, deep ulcers formed due to tumor necrosis. The patient eventually died of massive bleeding resulting from the major cervical vascular rupture caused by tumor necrosis and erosion. This case is novel and instructional, highlighting that apatinib might be effective, with manageable toxicity, for certain patients with refractory head and neck squamous cell carcinoma (HNSCC). The advantages and disadvantages of apatinib should be carefully evaluated, and close surveillance and quick intervention as required are critical to reduce fatal cancer-associated complications. The role of apatinib in recurrent or metastatic HNSCC needs to be clarified by multicenter trials in the near future.