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As one of the frequent complications leading to poor prognosis in hospitalized COVID-19 patients, a better understanding of venous thromboembolism (VTE) in COVID-19 patients is needed. We conducted a single-center, retrospective study on 96 COVID-19 patients admitted to the intensive care unit (ICU) from April to June 2022, in Shanghai Renji Hospital. Records of these COVID-19 patients upon admission were reviewed for demographic information, co-morbidities, vaccinations, treatment, and laboratory tests. VTE occurred in 11 (11.5%) cases among 96 COVID-19 patients despite the standard thromboprophylaxis since ICU admission. In COVID-VTE patients, a significant increase in B cells and a decrease in Ts cells were observed and a strong negative correlation ( r = −0.9524, P = .0003) was found between these two populations. In COVID-19 patients with VTE, increased MPV and decreased albumin levels were seen in addition to the common VTE indicators of D-dimer abnormalities. The altered lymphocyte composition in COVID-VTE patients is noteworthy. In addition to D-dimer, MPV and albumin levels might be novel indicators for the risk of VTE in COVID-19 patients.

Objective: Long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) participates in the regulation of non-small cell lung cancer (NSCLC) progression, but the underlying mechanisms are not fully revealed. This study aimed to determine the regulatory mechanism of FGD5-AS1 on the viability, migration, and invasion of NSCLC cells. Methods: QRT-PCR was performed to measure the expression of FGD5-AS1, microRNA-944 (miR-944), and MACC1 in NSCLC. The correlation between FGD5-AS1 and clinicopathological features of NSCLC patients was analyzed. The viability of NSCLC cells were detected using MTT assay, and the migration and invasion were measured by transwell assay. Additionally, dual-luciferase reporter assay was used to demonstrate the interactions among FGD5-AS1, miR-944, and MACC1. Furthermore, exosomes were isolated from NSCLC cells and identified by transmission electron microscopy (TEM) and western blot. Then, the macrophages treated with exosomes were co-cultured with NSCLC cells to assess the effect of exosomes containing lower FGD5-AS1 level on NSCLC. Results: The expression of FGD5-AS1 and MACC1 was increased in NSCLC, but miR-944 expression was decreased. FGD5-AS1 expression had significantly correlation with TNM stage and metastasis in NSCLC patients. FGD5-AS1 knockdown decreased the viability, migration, and invasion of NSCLC cells. Additionally, FGD5-AS1 and MACC1 were both targeted by miR-944 with the complementary binding sites at 3’ UTR. In the feedback experiments, miR-944 inhibition or MACC1 overexpression reversed the reduction effect of FGD5-AS1 knockdown on the tumorigenesis of NSCLC. Moreover, silencing of FGD5-AS1 suppressed macrophages M2 polarization, and eliminated the promoting effects of exosomes mediated macrophages on NSCLC cell migration and invasion. Conclusions: FGD5-AS1 knockdown attenuated viability, migration, and invasion of NSCLC cells by regulating the miR-944/MACC1 axis, providing a new therapeutic target for NSCLC.

Purposes: Minichromosome maintenance (MCM) proteins play an important role in replication and cell cycle progression. Even so, their expression and prognostic roles in cancer remain controversial. Methods: To address this issue, the study investigated the roles of MCMs in the prognosis of GC by using ONCOMINE, GEPIA2, UALCAN, Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, and DAVID databases. Results: Over expressions of mRNA and cell lines were found in all members of the MCM family, and MCMs were found to be significantly associated with pathological tumor grades in GC patients. Besides, higher mRNA expressions of MCM1/5/7 were found to be significantly associated with shorter overall survival (OS) and progression-free survival (FP) in GC patients, while higher mRNA expression of MCM4/6/9 were connected with favorable OS and FP. Moreover, a high mutation rate of MCMs (68%) was also observed in GC patients. Conclusions: The results indicated that MCM1/5/7 were potential targets of precision therapy for patients with GC. And MCM4/6/9 were new biomarkers for the prognosis of GC. The results of the study will contribute to supplement the existing knowledge, and help to explore therapeutic targets and enhance the accuracy of prognosis for patients with GC.

Summary: Background: Evidence from cohort studies in North America and Europe indicates that long-term exposure to fine particulate matter (PM2·5) is associated with an increased mortality risk. However, this association has rarely been quantified at higher ambient concentrations. We estimated the hazard ratio (HR) for all-cause mortality from long-term exposure to PM2·5 in a well established Chinese cohort of older adults. Methods: The Chinese Longitudinal Healthy Longevity Survey (CLHLS) is a prospective cohort study of men and women aged 65 years and older enrolled in 2008 and followed up through 2014 for mortality events. We studied individuals for whom residential locations were available in 2008 for linkage to 1 km grids of PM2·5 concentrations, derived from satellite remote sensing. Cox proportional hazards models were used to estimate the effect of long-term exposure to PM2·5 on all-cause mortality, controlling for age, sex, smoking status, drinking status, physical activity, body-mass index, household income, marital status, and education. We then used our results to estimate premature mortality related to PM2·5 exposure in the population aged 65 years and older in China in 2010. Findings: 13 344 individuals in the CLHLS cohort had data for all timepoints, yielding follow-up data for 49 440 person-years. In a 3-year window, these individuals were exposed to a median PM2·5 concentration of 50·7 μg/m3 (range 6·7–113·3). The overall HR for a 10 μg/m3 increase in this value was 1·08 (95% CI 1·06–1·09). In stratified analyses, HRs were higher in rural than in urban locations, in southern versus northern regions, and with exposure to lower versus higher PM2·5 concentrations. Based on the overall HR, we estimated that 1 765 820 people aged 65 years and older in China in 2010 had premature mortality related to PM2·5 exposure. Interpretation: Long-term exposure to PM2·5 is associated with an increased risk of all-cause mortality among adults aged 65 years and older in China, but the magnitude of the risk declines as the concentration of PM2·5 increases. Funding: National Natural Science Foundation of China, National High-Level Talents Special Support Plan of China for Young Talents, US National Aeronautics and Space Administration, and the Columbia University Global Policy Initiative.

Objective: This study was designed to evaluate the clinical application of preoperative auxiliary embolization for juvenile nasopharyngeal angiofibroma (JNA) by direct puncture embolization (DPE) of the tumor in combination with transarterial embolization (TAE). Methods: The study included 22 patients. An 18-gauge needle was used to puncture directly into the tumor, and 20-25 % N-butyl cyanoacrylate was injected under the guidance of fluoroscopy after confirming the placement of the needle into the JNA and no leaking into the surrounding tissue. Tumors were obstructed later via TAE. Results: The supplying arteries of JNA were from branches of the internal carotid and external carotid arteries. Control angiography showed the obliteration of contrast stain in the entire tumor mass and the distal supplying arteries disappeared after DPE in combination with TAE. Surgical resection was performed within 4 days after embolization and none of the patients required blood transfusion. Conclusions: The use of DPE in combination with TAE was a safe, feasible, and efficacious method. It can devascularize effectively the JNAs and reduce intraoperative bleeding when JNAs are extirpated. [ABSTRACT FROM AUTHOR]

Rabies is an acute zoonotic infectious disease caused by rabies virus. In 2015, the World Health Organization proposed the goal of eliminating dog-induced human rabies by 2030. In response to this goal positively, China has been dedicated to the control and elimination of rabies mainly caused by dogs, for nearly 10 years. By applying infectious disease dynamics, in this paper, we establish a dog-human rabies transmission model to forecast future epidemic trends of rabies, assess whether the goal of eliminating dog-induced human rabies cases in China can be achieved in 2030, and further evaluate and suggest the follow-up sustained preventive measures after the elimination of human rabies. By analyzing and simulating above dynamic model, it is concluded that rabies has been well controlled in China in recent years, but dog-induced human rabies cannot be eliminated by 2030 according to current situation. In addition, we propose to improve rabies control efforts by increasing the immunization coverage rate of rural domestic dogs, controlling the number of stray dogs and preventing the import of rabies virus in wild animals. Immunization coverage rate of rural domestic dogs which is currently less than 10% is far from requirement, and it needs to reach 50%-60% to meet the goal of 2030. Since it is difficult to immunize stray dogs, we suggest to control the number of stray dogs below 15.27 million to achieve the goal. If the goal of eliminating human rabies is reached in 2030, the essential immunization coverage needs to be maintained for 18 years to reduce the number of canine rabies cases to zero. Lastly, to prevent transmission of rabies virus from wild animals to dogs, the thresholds of the number of dogs and the immunization coverage rate of dogs after eliminating canine rabies cases are also discussed., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

We develop a new strategy for single-molecule monitoring of telomerase based on proximity ligation-transcription circuit-powered exponential amplifications. This strategy exhibits high sensitivity with a detection limit of 0.1 aM for the synthetic telomerase product TPC4 in vitro and 1 HeLa cell in vivo . Moreover, it can screen potential inhibitors, discriminate telomerase from interferents, and distinguish cancer cells from normal cells.

Background: Non-syndromic cleft lip and/or palate (NSCL/P) is a common maxillofacial birth defect, and the etiology of which is complex and still unclear. Accumulating studies indicate that long non-coding RNAs(lncRNAs) and microRNAs(miRNAs) play important roles in NSCL/P. However, the potential regulatory associations remain largely unknown. In this study, we screened differentially expressed miRNAs and constructed competing endogenous RNA (ceRNA) networks to lay a foundation for further research on the regulatory mechanism of ncRNAs in NSCL/P., Methods: NSCL/P plasma RNA was analyzed by miRNA sequencing. The bioinformatics database, GEO and STRING database, GO and KEGG enrichment analysis and Cytoscape software were used to analyze and screen lncRNAs and mRNAs potentially related to differential miRNAs. The expression levels of lncRNA, miRNA and mRNA in ceRNA network were detected by RT-qPCR., Results: In NSCL/P plasma samples, there were 47 differentially expressed miRNAs in CPO group and 36 differentially expressed miRNAs in CL/P group. GO and KEGG enrichment analysis showed that cell cycle, cell response to DNA damage stimulation, and the TGF-βsignaling pathway were relevant to the formation of NSCL/P. The RT-qPCR results showed that the expression levels of lncRNA NEAT1, hsa-miR-130 b-3p, hsa-miR-212-3p, hsa-miR-200 b-3p and SMAD2 were different in NSCL/P., Conclusions: We found that differentially expressed miR-212-3p, miR-200 b-3p and miR-130 b-3p may be involved in the pathogenesis of cleft palate by regulating related target genes., Competing Interests: Declaration of competing interest The authors deny any conflicts of interest related to this study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: We present our experience with transoral segmental mandibulectomy, in conjunction with vascularized osseous mandibular reconstruction, utilizing an intraoral anastomosis and free of extraoral incisions. Virtual surgical planning and intraoperative navigation were used to help achieve this minimally invasive and scar-free approach., Methods: A retrospective study was performed on 9 patients who underwent transoral segmental mandibulectomy followed by vascularized osseous reconstruction using an intraoral anastomosis between January 2018 and October 2018. The anastomotic recipient vessels were the facial artery and vein. The outcome variable was defined as the flap survival. Postoperative panoramic radiographs and computed tomography images were obtained for assessment of the neo-mandible. In addition, we performed a cadaver dissection to highlight relevant anatomic details of the facial artery and vein., Results: Successful transoral segmental mandibulectomy was achieved in 9 patients, with an intraoral anastomosis successfully achieved in 8 patients. In one patient, an extraoral anastomosis was required because of challenging facial vein anatomy. Both recipient and donor sites healed uneventfully with a 100% successful rate of flap survival. In all cases, a well-positioned neo-mandible with good occlusion was demonstrated on postoperative imaging and examination. A symmetric facial appearance with no restrictions in mouth opening was also achieved in each case. In our cadaver dissection, we describe the anatomical course of the facial artery and vein. An average angle of 30° between these vessels is identified., Conclusions: Transoral segmental mandibulectomy combined with intraoral microvascular mandibular reconstruction is a surgically achievable technique with the benefit of being scar free., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: This study aims to explore the association between life events and coping styles, and how resilience and self-esteem mediate the association. Methods: A cross-sectional study was conducted among 981 left-behind adolescents (LBAs) in five junior high schools in Hunan Province, China, from April 13 to April 20, 2020. We utilized self-designed sociodemographic questionnaire, Adolescent Self-Rating Life Events Checklist, Resilience Scale Chinese Adolescent, Rosenberg Self-Esteem Scale, and Simplified Coping Style Questionnaire to assess the mental health of LBAs. Statistic description, Pearson correlation analysis, and structural equation model were adopted to analyze the data. Results: Results revealed that life events could negatively predict resilience (β = -0.29, P < 0.001) and self-esteem (β = -0.39, P < 0.001) and positively predict LBAs' positive coping style (β = 0.28, P < 0.001) and negative coping style (β = 0.21, P < 0.001). Self-esteem could also positively predict the resilience of LBAs (β = 0.62, P < 0.001); resilience could negatively predict the negative coping style (β = -0.21, P < 0.001) and positively predict the positive coping style (β = 0.79, P < 0.001). Life events not only have direct effects on negative coping style (β = 0.21) and positive coping style (β = 0.28) but also have indirect effects on coping styles by affecting resilience (β = -0.29) and self-esteem (β = -0.39). The total effect of life events on coping styles was 0.32, where 34.37% was mediated by resilience and self-esteem. Conclusion: We proved that resilience and self-esteem mediated most of the effects of life events on coping styles. The findings had important implications for interventions to promote mental health of LBAs, particularly the enhancement of resilience and self-esteem., (Copyright © 2020 Li, Chen, Zhang, Lv, Välimäki, Li, Yang, Tao, Ye, Tan and Zhang.)

DNA nanowalkers moving progressively along a prescribed DNA track are useful tools in biosensing, molecular theranostics and biosynthesis. However, stochastic DNA nanowalkers that can perform in living cells have been largely unexplored. We report the development of a novel stochastic bipedal DNA walker that, for the first time, realizes direct intracellular base excision repair (BER) fluorescence activation imaging. In our design, the bipedal walker DNA was generated by BER-related human apurinic/apyrimidinic endonuclease 1 (APE1)-mediated cleavage of DNA sequences at an abasic site in the intracellular environment, and it autonomously travelled on spherical nucleic acid (SNA) surfaces via catalyzed hairpin assembly (CHA). Our nanomachine outperforms the conventional single leg-based DNA walker with an improved sensitivity, kinetics and walking steps. Moreover, in contrast to the single leg-based DNA walker, the bipedal DNA walker is capable of monitoring the fluorescence signal of reduced APE1 activity, thus indicating amplified intracellular imaging. This bipedal DNA-propelled DNA walker presents a simple and modular amplification mechanism for intracellular biomarkers of interest, providing an invaluable platform for low-abundance biomarker discovery leading to the accurate identification and effective treatment of cancers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A well-defined 3D DNA nanostructure with precise composition was developed by stoichimetric combination of a DNA tetrahedron and Y-shaped DNA, which allowed multiplexed, signal-amplified fluorescence imaging of miRNAs in living cells via hybridization chain reaction.

Objectives: The activation of the adenosine A3 receptor (A3AR) can regulate inflammation, but the way that this regulates colonic mucosal inflammation in ulcerative colitis (UC) remains unclear. This study aimed at examining A3AR expression and investigating the effect of A3AR activation on ex vivo cytokine expression and nuclear factor-kappa B (NF-κB) signaling in colonic mucosa., Methods: Colonic mucosal biopsied tissue from 18 patients with UC and 11 healthy controls was tested for A3AR expression by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot. Following treatment for 24 hours with or without 2-Cl-IB-MECA, an A3AR agonist, TNF-α and IL-1β secreted by the cultured colonic mucosal tissue were quantified by ELISA. The colonic mucosal epithelia were dissected and treated with, or without 2-Cl-IB-MECA for 24 hours. The NF-κB p65 protein and its distribution in the cultured colonic epithelia were examined by immunofluorescence and Western blot., Results: Compared with the controls, down-regulated A3AR expression and up-regulated TNF-α and IL-1β production and NF-κB p65 protein were observed in the UC colonic mucosa. The activation of A3AR by 2-Cl-IB-MECA significantly decreased TNF-α and IL-1β production and attenuated the NF-κB p65 activation in colonic tissues from patients with UC., Conclusions: A3AR activation inhibited inflammation by mitigating pro-inflammatory cytokine production and the NF-κB signal activation in colonic mucosa of patients with UC. A3AR activation may play a role in the pathogenesis of UC., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

An ultrasensitive enzyme-free electrochemical sandwich DNA biosensor is described for the detection of ssDNA oligonucleotides. A DNA sequence derived from the genom of Helicobacter pylori was selected as a model target DNA. The DNA assay was realized through catching target DNA on capture DNA immobilized gold electrode; then labeling the target DNA with reporter DNA (rpDNA) and initiator DNA (iDNA) co-modified gold nanoparticles (AuNPs). The high density of iDNAs serves as one of the amplification strategies. The iDNA triggers hybridization chain reaction (HCR) between two hairpins. This leads to the formation of a long dsDNA concatamer strand and represents one amplification strategy. The electrochemical probe [Ru(NH 3 ) 5 L] 2+ , where L stands for 3-(2-phenanthren-9-ylvinyl)pyridine, intercalated into dsDNA chain. Multiple probe molecules intercalate into one dsDNA chain, serving as one amplification strategy. The electrode was subjected to differential pulse voltammetry for signal acquisition, and the oxidation peak current at -0.28 V was recorded. On each AuNP, 240 iDNA and 25 rpDNA molecules were immobilized. Successful execution of HCR at the DNA-modified AuNPs was confirmed by gel electrophoresis and hydrodynamic diameter measurements. Introduction of HCR significantly enhances the DNA detection signal intensity. The assay has two linear ranges of different slopes, one from 0.01 fM to 0.5 fM; and one from 1 fM to 100 fM. The detection limit is as low as 0.68 aM. Single mismatch DNA can be differentiated from the fully complementary DNA. Conceivably, this highly sensitive and selective assay provides a general method for detection of various kinds of DNA. Graphical abstractSchematic representation of the detection and the amplification principles of the electrochemical sandwich DNA assay. Purple curl: Captured DNA; Green curl: Reporter DNA; Orange curl: HCR initiator DNA; Yellow solid-circle: Gold nanoparticle; H1 and H2: Two hairpin DNA; [Ru(NH 3 ) 5 L] 2+ : Signal probe.

The development of electronic technology has attracted attention on the biological effects of electromagnetic fields (EMFs) and electromagnetic pulse (EMP). It remains controversial whether EMP irradiation is neurotoxic or beneficial for recovery from injuryies such as cerebral ischemia. Microglia is innate immune cells in the brain, exhibiting either neurotoxicity or neuroprotection effect during various central nervous system diseases, depending on their activation into a classical (M1) or alternative (M2) phenotype, respectively. The Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NFκB) pathway is important for microglia activation. In this study, we investigated the effect of EMP on neuronal apoptosis and microglia polarization in vivo and in vitro, using an EMP of 400 kV/m and 1 hertz for 200 pulses. Short EMP irradiation (≤24 h) resulted in microglial conversion from the resting to the M1-type state, activation of the TLR4/MyD88/NFκB pathway, higher levels of inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor-α, as well as neuronal apoptosis induction. In contrast, long EMP irradiation (3 days) resulted in microglial activation into the M2-type, decreased apoptosis and inflammatory mediator production, and increased levels of the neuroprotective effectors IL-10, transforming growth factor beta, and brain-derived neurotrophic factor. EMP induces both neuronal damage and neuronal recovery by influencing the switch of M1/M2 polarization and the TLR4/MyD88/NFκB pathway., (Copyright 2019 Biolife Sas. www.biolifesas.org.)

A novel self-assembled protein-scaffolded CRISPR-Cas9 nanosystem for facile and efficient gene editing in a DNAzyme-controlled manner has been developed.

Aims and Objectives: To determine the effect of a transtheoretical model (TTM)-based intervention on patients with an ostomy and provide patient-centred, accessible assistance and dynamic education to improve patient self-management., Background: Proper self-management may promote the rehabilitation of patients with an ostomy. TTM-based interventions have resulted in positive health behavioural changes., Design: Randomised controlled trial performed according to the CONSORT guidelines., Subject and Setting: The sample comprised 55 men and 37 women (24-77 years old, mean ± SD = 52.8 ± 11.13 years). The study settings included three tertiary hospitals in Changsha, Hunan, China., Methods: The 92 patients, recruited from August 2012 to March 2013, were randomised into a control group and an intervention group. Randomisation was done by using a block randomisation list with a block size of 4. Self-management behaviours were assessed at the baseline, 2 days before discharge and after 1, 3 and 6 months of follow-up. The chi-squared test, independent sample t test and repeated measures analysis of variance were used to analyse the data., Results: Patients in the intervention group were more likely to be at the action and maintenance stages compared with those in the control group. We also observed significant improvements in the self-management ability in the process of change, the decisional balance and self-efficacy in the intervention group compared with those in the control group after four intervention sessions and up to 6 months of follow-up. No serious intervention-related adverse events were observed., Conclusions: The TTM-based intervention had positive effects on self-management behaviours of patients with an ostomy., Relevance to Clinical Practice: The TTM-based intervention had positive effects on self-management behaviours of patients with an ostomy and may provide a reference for health providers to develop behaviour promotion programmes to improve the self-management of patients with an ostomy., (© 2018 John Wiley & Sons Ltd.)

Electromagnetic pulse (EMP) is a unique type of electromagnetic radiation, and EMP exposure causes a series of biological effects. The nervous system is sensitive to EMP. We studied the neuroprotective effects of isoflurane preconditioning against EMP exposure and used hematoxylin-eosin staining (HE) to observe the effects of electromagnetic pulse and isoflurane preconditioning on neurons. Inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the expression of caspase-3, CD11b, TLR4, and NF κ Bp65. We found that after EMP exposure, the number of abnormal neurons had increased, and the expression of caspase-3, CD11b, TLR4, and NF κ Bp65 had also increased. Isoflurane preconditioning can reverse the above phenomenon. Moreover, we found that isoflurane preconditioning can reduce neuronal apoptosis and improve cognitive impairment induced by EMP. These findings indicate that isoflurane preconditioning can protect neurons in the cerebral cortex from EMP exposure, alleviate the inflammatory reaction and cell apoptosis, and improve cognitive impairment induced by EMP. These effects may occur through the downregulation of the TLR4/NF κ B signaling pathway and the inhibition of microglial activation.

Hyperkalemia is a life-threatening emergency in maintenance hemodialysis (MHD) patients. This clinical trial investigated the efficacy and safety of calcium-polystyrene sulfonate (Ca-PS) in MHD patients with interdialytic hyperkalemia. A total of 58 hemodialysis patients with hyperkalemia (≥5.5 mol/L) were selected and administered either a 3-week Ca-PS (3 × 5 g/day) or a blank control following the model of a prospective, randomized, crossover clinical trial with a 1-week washout period. All patients were followed up for another 3 weeks for safety evaluations. The primary outcome was the magnitude of the change in serum potassium levels. The secondary outcomes were electrocardiography (ECG) changes and treatment safety (volume overload, electrolyte imbalance). Compared with the control group, Ca-PS treatment significantly reduced serum potassium levels (P <0.01). More patients in the Ca-PS group had lower serum potassium levels than the safety level of <5.5 mmol/L (32% for control vs. 61% for Ca-PS, P <0.01). Peaked T-wave occurred less frequently in patients in the Ca-PS group (13.8% for Ca-PS vs. 31.03% for control, P <0.01). In addition, Ca-PS reduced serum phosphorus levels with no effects on serum levels of calcium and sodium, fluid volume, blood pressure, or interdialytic weight gain. Ca-PS treatment decreases serum levels of potassium and phosphorus in MHD patients with interdialytic hyperkalemia. Ca-PS does not induce volume overload or disrupt electrolyte balance., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Treatment of large bone defects represents a major clinical problem worldwide. Suitable bone substitute materials are commonly required to achieve successful bone regeneration, and much effort has been spent to optimize their chemical compositions, 3D architecture and mechanical properties. However, material-immune system interactions are increasingly being recognized as a crucial factor influencing regeneration. Here, we envisioned an accurate and proactive immunomodulation strategy via delivery of IL-4 (key regulator of macrophage polarization) to promote bone substitute material-mediated regeneration. Methods : Four different IL-4 doses (0 ng, 10 ng, 50 ng and 100 ng) were delivered into rat large cranial bone defects at day 3 post-operation of decellularized bone matrix (DBM) material implantation, and the osteogenesis, angiogenesis and macrophage polarization were meticulously evaluated. Results: Micro-CT analysis showed that immunomodulation with 10 ng IL-4 significantly outperformed the other groups in terms of new bone formation (1.23-5.05 fold) and vascularization (1.29-6.08 fold), achieving successful defect bridging and good vascularization at 12 weeks. Histological analysis at 7 and 14 days showed that the 10 ng group generated the most preferable M1/M2 macrophage polarization profile, resulting in a pro-healing microenvironment with more IL-10 and less TNF-α secretion, a reduced apoptosis level in tissues around the materials, and enhanced mesenchymal stem cell migration and osteogenic differentiation. Moreover, in vitro studies revealed that M1 macrophages facilitated mesenchymal stem cell migration, while M2 macrophages significantly increased cell survival, proliferation and osteogenic differentiation, explaining the in vivo findings. Conclusions: Accurate immunomodulation via IL4 delivery significantly enhanced DBM-mediated osteogenesis and angiogenesis via the coordinated involvement of M1 and M2 macrophages, revealing the promise of this accurate and proactive immunomodulatory strategy for developing new bone substitute materials., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

A novel DNAzymatic amplifier nanomachine that is reconstructed in response to an mRNA input has been developed to enable the functions of concurrent sensitive mRNA imaging and activatable gene therapy in living cells.

With the advance of sequencing technology, the number of sequenced plant genomes has been rapidly increasing. However, understanding of the gene function in these sequenced genomes lags far behind; as a result, many coding plant sequences in public databases are annotated as proteins with domains of unknown function (DUF). Function of a protein family DUF810 in rice is not known. In this study, we analysed seven members of OsDU810 (OsDUF810.1-OsDUF810.7) family with three distinct motifs in rice Nipponbare. By phylogenetic analysis, OsDUF810 proteins fall into three major groups (I, II, III). Expression patterns of the seven corresponding OsDUF810 protein-encoding genes in 15 different rice tissues vary. Under drought, salt, cold and heat stress conditions and ABA treatment, the expression of OsDUF810.7 significantly increases. Overexpression of this protein in E. coli lead to a significant enhancement of catalase (CAT) and peroxidase (POD) activities, and improved bacterial resistance to salt and drought.

Aspergoterpenins A⁻D ( 1 ⁻ 4 ), four new bisabolane sesquiterpenoid derivatives, were obtained from the endophytic fungus, Aspergillus versicolor , together with eight known compounds ( 5 ⁻ 1 2 ), and their structures were elucidated by a comprehensive analysis of their NMR (Nuclear Magnetic Resonance), MS (Mass Spectrum) and CD (Circular Dichroism) spectra. Aspergoterpenin A ( 1 ) was the first example with a characteristic ketal bridged-ring part in the degraded natural bisabolane-type sesquiterpene structures. The compounds 1 ⁻ 1 2 displayed no significant activities against four cancer cell lines (A549, Caski, HepG2 and MCF-7). Further, the antimicrobial activities to Erwinia carotovora sub sp. Carotovora were evaluated, and the results showed that compounds 1 ⁻ 1 2 displayed antimicrobial activities with MIC values ranging from 15.2 to 85.2 μg/mL.

Since diabetes lead to alterations in bone metabolism with reductions in bone mineral content and delayed bone formation, the most effective method for bone regeneration in diabetes remains to be determined. In this study, type 2 diabetes were successfully induced via a high-fat diet and low-dose streptozotocin intraperitoneal injection. Excess reactive oxygen species (ROS) has been implicated in diabetes mellitus. Overexpression of ROS can lead to oxidative stress and subsequently to H 2 O 2 -mediated impaired proliferation and delayed cellular differentiation. As a result, antioxidant alpha-lipoic acid (ALA)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres were fabricated using the emulsion solvent evaporation method, and a sustained and controlled release of ALA was observed up to 27 days. It was demonstrated that biodegradable PLGA microspheres loaded with ALA acted as ROS scavengers and partially recover the mesenchymal stem cell proliferation and differentiation. The bone formation of ALA loaded scaffolds in rat cranial bone defects were greater than the prime three-dimensional collagen scaffold. These results suggest the application of ALA loaded PLGA microsphere exhibit good bioactivity and bone forming ability in diabetes., Competing Interests: None., (IJCEP Copyright © 2017.)

Objective: To observe and evaluate the effect of dexmedetomidine on the perioperative immune function of patients undergoing a radical mastectomy., Patients and Methods: 124 patients undergoing radical mastectomy were divided into the observation group (treated with dexmedetomidine) and the control group (treated with saline) by randomized digital table and double blinded and randomized design. 10 min before anesthesia induction, the patients in the observation group were injected with dexmedetomidine 0.1 ug.kg-1.min-1. The injection of 0.9% sodium chloride solution was given to the control group at the same rate. In the experiment, the medications of anesthesia induction and anesthesia maintain were identical. Venous blood at five times: T0 (before anesthesia), T1 (6 h after surgery), T2 (24 h after surgery), T3 (48 h after surgery), T4 (72 h after surgery) were collected. ELISA (Enzyme Linked Immunosorbent Assay) was used to detect concentrations of IL-2, IFN-γ, IL-4, IL-6 and IL-10; FACS flow cytometry was used to determine the level of T-lymphocyte subsets (CD3+, CD4+, CD8+) and NK cells., Results: Compared with the control group, the cell levels of CD3+ and CD4+ in the observation group rose remarkably at T3 and T2 (p<0.05). The cell level of CD8+ fell at T2 with significant difference; NK cell level increased noticeably at T1 and T2, and CD4+/CD8+ rose dramatically at all postoperative time points. Obviously, the patients' immune function, to some extent, has been affected; in addition, the concentration of INF-γ in observation group increased prominently at T1, T2 and T3 (p<0.05), and the concentration of IL-2 at T2, IL-10 at T1 and T2, and IL-6 at T2 and T3 in the observation group all rose significantly (p<0.05), and less cytokine Th1 drifted to Th2., Conclusions: The dexmedetomidine can effectively maintain the homeostasis of cell immune function of patients undergoing a radical mastectomy.

Background: We conducted a retrospective analysis of the clinical outcomes and evaluated the reconstructive strategies in patients who underwent secondary maxillary reconstruction with a vascularized fibula osteomyocutaneous flap (VFOF)., Methods: From May of 2001 to June of 2014, 34 patients who underwent secondary maxillary reconstruction with VFOF, with or without titanium mesh, were reviewed. The patients were divided into two groups of maxillary reconstruction, according to different planning and treatment strategies. In Group 1, presurgical planning was achieved using three-dimensional stereomodeling (n = 12). In Group 2, virtual surgical planning was performed and guided templates were produced (n = 22). The differences in the preoperative planning, intraoperative technique, postoperative complications, and long-term results between the two groups were analyzed. Statistical analysis was performed to determine the differences between the two groups and the risk factors for prognosis., Results: Similar and accurate secondary maxillary reconstructions were successfully performed in Group 1 and 2. Postoperative complications were reported in 8 patients in Group 1 and 11 patients in Group 2. Complications were reported in patients who underwent radiotherapy. The incidence of postoperative complications in Group 2 were lower than that in Group 1 with the exception of midfacial collapse (P > 0.05). The long-term results of some patients with class 3 defects were not satisfactory because of midfacial collapse and lower eyelid ectropion. Stepwise regression analysis showed radiotherapy to be a risk factor for prognosis., Conclusions: The long-term results of secondary maxillary reconstruction were reported to be acceptable in our study. Radiotherapy was the risk factor for prognosis in secondary maxillary reconstruction. On the basis of these results, we highly recommend our strategy for secondary maxillary reconstruction. Good functional results could be achieved after the accurate restoration of maxillary alveolar ridge with several fibular segments using virtual surgical planning and dental restoration., (Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Penicitroamide ( 1 ), a new metabolite with a new framework, was isolated from the ethyl acetate extract of the PDB (Potato Dextrose Broth) medium of Penicillium sp. (NO. 24). The endophytic fungus Penicillium sp. (NO. 24) was obtained from the healthy leaves of Tapiscia sinensis Oliv. The structure of penicitroamide ( 1 ) features a bicyclo[3.2.1]octane core unit with a high degree of carbonylization (four carbonyl groups and one enol group). The chemical structure of penicitroamide ( 1 ) was elucidated by analysis of 1D-, 2D-NMR and MS data. In bioassays, penicitroamide ( 1 ) displayed antibacterial potency against two plant pathogens, Erwinia carotovora subsp. Carotovora (Jones) Bersey, et al. and Sclerotium rolfsii Sacc. with MIC 50 at 45 and 50 μg/mL. Compound 1 also showed 60% lethality against brine shrimp at 10 μg/mL. Penicitroamide ( 1 ) exhibited no significant activity against A549, Caski, HepG2 and MCF-7 cells with IC 50 > 50 μg/mL. Finally, the possible biosynthetic pathway of penicitroamide ( 1 ) was discussed.

Breast cancer (BCa) is one of the major deadly cancers in women. However, treatment of BCa is still hindered by the acquired-drug resistance. It is increasingly reported that exosomes take part in the development, metastasis, and drug resistance of BCa. However, the specific role of exosomes in drug resistance of BCa is poorly understood. In this study, we investigate whether exosomes transmit drug resistance through delivering miR-222. We established an adriamycin-resistant variant of Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line (MCF-7/Adr) from a drug-sensitive variant (MCF-7/S). Exosomes were isolated from cell supernatant by ultracentrifugation. Cell viability was assessed by MTT assay and apoptosis assay. Individual miR-222 molecules in BCa cells were detected by fluorescence in situ hybridization (FISH). Then, FISH was combined with locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH). Individual miR-222 could be detected as bright photostable fluorescent spots and then the quantity of miR-222 per cell could be counted. Stained exosomes were taken in by the receipt cells. MCF-7/S acquired drug resistance after co-culture with exosomes from MCF-7/Adr (A/exo) but did not after co-culture with exosomes from MCF-7/S (S/exo). The quantity of miR-222 in A/exo-treated MCF-7/S was significantly greater than in S/exo-treated MCF-7/S. MCF-7/S transfected with miR-222 mimics acquired adriamycin resistance while MCF-7/S transfected with miR-222 inhibitors lost resistance. In conclusion, exosomes are effective in transmitting drug resistance and the delivery of miR-222 via exosomes may be a mechanism.

Transport through the cell membrane can be divided into active, passive and vesicular types (exosomes). Exosomes are nano-sized vesicles released by a variety of cells. Emerging evidence shows that exosomes play a critical role in cancers. Exosomes mediate communication between stroma and cancer cells through the transfer of nucleic acid and proteins. It is demonstrated that the contents and the quantity of exosomes will change after occurrence of cancers. Over the last decade, growing attention has been paid to the role of exosomes in the development of breast cancer, the most life-threatening cancer in women. Breast cancer could induce salivary glands to secret specific exosomes, which could be used as biomarkers in the diagnosis of early breast cancer. Exosome-delivered nucleic acid and proteins partly facilitate the tumorigenesis, metastasis and resistance of breast cancer. Exosomes could also transmit anti-cancer drugs outside breast cancer cells, therefore leading to drug resistance. However, exosomes are effective tools for transportation of anti-cancer drugs with lower immunogenicity and toxicity. This is a promising way to establish a drug delivery system., (© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Objective: Arteriovenous malformations (AVMs) involving the periorbital region are technically challenging clinical entities to manage. The purpose of the present study was to present our initial experience of ethanol embolization in a series of 16 patients with auricular AVMs and assess the outcomes of this treatment., Methods: Transcatheter arterial embolization and/or direct percutaneous puncture embolization were performed in the 16 patients. Pure or diluted ethanol was manually injected. The follow-up evaluations included physical examination and angiography at 1- to 6-month intervals., Results: During the 28 ethanol embolization sessions, the amount of ethanol used ranged from 2 to 65 mL. The obliteration of ulceration, hemorrhage, pain, infection, pulsation, and bruit in most of the patients was obtained. The reduction of redness, swelling, and warmth was achieved in all the 16 patients, with down-staging of the Schobinger status for each patient. AVMs were devascularized 100 % in 3 patients, 76-99 % in 7 patients, and 50-75 % in 6 patients, according to the angiographic findings. The most common complications were necrosis and reversible blister. No permanent visual abnormality was found in any of the cases., Conclusion: Ethanol embolization is efficacious and safe in the treatment of AVMs in the periorbital region and has the potential to be accepted as the primary mode of therapy in the management of these lesions.

Introduction: Previous studies have produced controversial results regarding whether mesenchymal stem cells (MSCs) promote or inhibit tumor development. Given the dual role of MSCs in inflammation and cancer, in this study the colitis-associated colorectal cancer (CAC) model was used to examine whether umbilical cord tissue-derived MSCs could prevent neoplasm by inhibiting chronic inflammation., Methods: MSCs were obtained and identified using flow cytometry. Colitis-associated colorectal cancer model was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) and MSCs were injected intravenously twice. Levels of immune cells in mesenteric lymph node including regulatory T (Treg) cells were detected using flow cytometry. Naïve T cells and Jurkat cells were co-cultured with MSCs and the effect of MSCs on Treg cells differentiation was evaluated., Results: After injection through tail vein, MSCs could migrate to colon and suppress colitis-related neoplasm. This tumor suppressive effect was characterized by longer colon length, decreased tumor numbers and decreased expression of Ki-67. Moreover, MSCs alleviated the pathology of inflammation in the colitis stage of CAC model and inhibited inflammation cytokines both in colon and serum. Furthermore, Treg cells were accumulated in mesenteric lymph node of MSCs-treated mice while the percentage of T helper cells 2 (Th2) and Th17 were not changed. Of note, MSCs secreted transforming growth factor-β (TGF-β) enhanced the induction of Treg cells from naïve T cells. The conditioned medium of MSCs also activated Smad2 signaling, which has been reported to regulate Treg cells., Conclusions: These results proved that MSCs could migrate to colon tissues and induce the differentiation of Treg cells via Smad2 as so to inhibit the colitis and suppress the development of CAC.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expressions at posttranscriptional level. Growing evidence points to their significant role in the acquisition of drug resistance in cancers. Studies show that miRNAs are often aberrantly expressed in human cancer cells which are associated with tumorigenesis, metastasis, invasiveness, and drug resistance. Breast cancer is the leading cause of cancer-induced death in women. Over the last decades, increasing attention has been paid to the effects of miRNAs on the development of breast cancer drug resistance. Among them, miR-155 takes part in a sequence of bioprocesses that contribute to the development of such drug resistance, including repression of FOXO3a, enhancement of epithelial-to-mesenchymal transition (EMT) and mitogen-activated protein kinase (MAPK) signaling, reduction of RhoA, and affecting the length of telomeres. In this review, we discuss the role of miR-155 in the acquisition of breast cancer drug resistance. This will provide a new way in antiresistance treatment of drug-resistant breast cancer.

Acquired drug resistance is a major obstacle to chemotherapy of cancers. In this study, we aim to investigate the role of exosomes in drug-resistance transfer between breast cancer cells and detect the probable mechanism. A docetaxel-resistant variant of MCF-7 cell line (MCF-7/DOC) was established and then compared with the drug-sensitive variant (MCF-7/S). Exosomes were expelled from the cell supernatant using ultracentrifugation. Drug resistance was assessed by apoptosis assay and MTT examination. Expressions of P-glycoprotein (P-gp) were analyzed by flow cytometry. Stained exosomes were absorbed by receipt cells. MCF-7/S in the presence of exosomes extracted from the supernatant of MCF-7/DOC (DOC/exo) acquired drug resistance, while MCF-7/S exposed to their own exosomes (S/exo) did not. P-gp expression patterns of exosomes were similar as the originated cells. P-gp expression of MCF-7/S increased after incubation with DOC/exo and was affected by the amount of exosomes. Exosomes are effective in transferring drug resistance as well as P-gp from drug-resistant breast cancer cells to sensitive ones. The delivery of P-gp via exosomes may be a mechanism of exosome-mediated drug resistance transfer.

Breast cancer (BCa) remains chemo-unresponsive by inevitable progression of resistance to first-line treatment with docetaxel (doc). Emerging studies indicate that exosomes act as mediators of intercellular communication between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development. Such modulatory effects have been related to the constant shuttle of biologically active molecules including microRNAs (miRNAs). Here, we aimed to investigate the relevance of exosome-mediated miRNA delivery in resistance transmission of BCa subpopulations. Using microarray and polymerase chain reaction, we found that exosomes from doc-resistant BCa cells (D/exo) loaded cellular miRNAs. Following D/exo transfer to the fluorescent sensitive cells (GFP-S), some miRNAs were significantly increased in recipient GFP-S. Target gene prediction and pathway analysis revealed the involvement of the top 20 most abundant miRNAs of D/exo in pathways implicated in therapy failure. Coculture assays showed that miRNA-containing D/exo increased the overall resistance of GFP-S to doc exposure. Moreover, D/exo was able to alter gene expression in GFP-S. Our results open up an intriguing possibility that drug-resistant BCa cells may spread chemoresistance to sensitive ones by releasing exosomes and that the effects could be partly attributed to the intercellular transfer of specific miRNAs.

The molecular basis for group I metabotropic glutamate receptors (mGluR1 and 5) coupling to membrane ion channels and intracellular calcium pools is not fully understood. Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. In the present study, we demonstrate that Homer1b/c is constitutively expressed in PC12 cells, whereas Homer1a, the immediate early gene product, can be up-regulated by brain derived neurotrophic factor (BDNF) and glutamate. Knockdown of Homer1b/c using specific target small interfering RNA (siRNA) did not interfere the expression of mGluR1, mGluR5 and their downstream effectors, including inositol-1,4,5-trisphosphate receptors (IP3R), phospholipase C (PLC) and Gq proteins. By analyzing Ca(2+) imaging in PC12 cells, we demonstrated that Homer1b/c is an essential regulator of the Ca(2+) release from the endoplasmic reticulum (ER) induced by the activation of group I mGluRs, IP3R and ryanodine receptors (RyR). Furthermore, the group I mGluRs activation-dependent refilling of the Ca(2+) stores in both resting and depolarizing conditions were strongly attenuated in the absence of Homer1b/c. Together, our results demonstrate that in PC12 cells Homer1b/c is a regulator of group I mGluRs related Ca(2+) homeostasis that is essential for the maintenance of normal Ca(2+) levels in the ER., (Copyright © 2014 Elsevier Inc. All rights reserved.)

MicroRNA-452 (miRNA-452) was overexpressed in docetaxel-resistant human breast cancer MCF-7 cells (MCF-7/DOC). However, its role in modulating the sensitivity of breast cancer cells to docetaxel (DOC) remains unclear. The aim of this study is to investigate the role of miRNA-452 in the sensitivity of breast cancer cells to DOC.Real-time quantitative PCR (RT-qPCR) were used to identify the differential expression of miRNA-452 between MCF-7/DOC and MCF-7 cells. MiRNA-452 mimic was transfected into MCF-7 cells and miRNA-452 inhibitor was transfected into MCF-7/DOC cells. The role of miRNA-452 in these transfected cells was evaluated using RT-qPCR, MTT assay, and flow cytometry assay. The relationship of miRNA-452 and its predictive target gene "anaphase-promoting complex 4" (APC4) was analyzed by RT-qPCR and Western blot.MiRNA-452 showed significantly higher expression (78.9-folds) in MCF-7/DOC cells compared to parental MCF-7 cells. The expression of miRNA-452 in the mimic transfected MCF-7 cells was upregulated 212.2-folds (P < 0.05) compared to its negative control (NC), and the half maximal inhibitory concentration (IC50) value of DOC (1.98 ± 0.15 μM) was significantly higher than that in its NC (0.85 ± 0.08 μM, P < 0.05) or blank control (1.01 ± 0.19 μM, P < 0.05). Furthermore, its apoptotic rate (6.3 ± 1.3 %) was distinctly decreased compared with that in its NC (23.8 ± 6.6 %, P < 0.05) or blank control (18.6 ± 4.7 %, P < 0.05). In contrast, the expression of miRNA-452 in the inhibitor-transfected MCF-7/DOC cells was downregulated 0.58-fold (P < 0.05) compared to its NC, the IC50 value of DOC (44.5 ± 3.2 μM) was significantly lower than that in its NC (107.3 ± 6.63 μM, P < 0.05) or blank control (102.22 ± 11.34 μM, P < 0.05), and the apoptotic rate (45.5 ± 10.8 %) was distinctly increased compared with its NC (9.9 ± 2.2 %, P < 0.05) and blank control (9.4 ± 2.5 %, P < 0.05). Further, there was an inverse association between miRNA-452 and APC4 expression in breast cancer cells in vitro.Dysregulation of miRNA-452 involved in the DOC resistance formation of breast cancer cells may be, in part, via targeting APC4.

A gold nanoparticle (GNP) probe-based assay (GNPA) modified from the bio-barcode assay (BCA) was developed for ultrasensitive detection of ricin, a potential biothreat agent. In the GNPA, a chain of ricin was captured by a GNP probe coated with polyclonal antibodies and single-stranded signal DNA. A magnetic microparticle (MMP) probe coated with ricin A chain monoclonal antibody was then added to form an immuno-complex. After being magnetically separated, the immuno-complex containing the single-stranded signal DNA was characterized by PCR and real-time PCR. A detection limit of 10(-2) fg/ml was determined for the ricin A chain; this is eight orders of magnitude more sensitive than that achieved with an ELISA and two orders more sensitive than that obtained with the BCA. The coefficients of variation (CV) of the intra- and inter-assay values ranged from 3.82-6.46%. The results here show that this novel assay is an ultrasensitive method for detection of ricin proteins and may be suitable for the ultrasensitive detection of other proteins.

Adriamycin and docetaxel are two agents commonly used in treatment of breast cancer, but their efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. Here we reinforced other's report that human breast cancer cell line MCF-7/S could acquire increased survival potential from its resistant variants MCF-7/Adr and MCF-7/Doc. Additionally, exosomes of the latter, A/exo and D/exo, significantly modulated the cell cycle distribution and drug-induced apoptosis with respect to S/exo. Exosomes pre-treated with RNase were unable to regulate cell cycle and apoptosis resistance, suggesting an RNA-dependent manner. Microarray and polymerase chain reaction for the miRNA expression profiles of A/exo, D/exo, and S/exo demonstrated that they loaded selective miRNA patterns. Following A/exo and D/exo transfer to recipient MCF-7/S, the same miRNAs were significantly increased in acquired cells. Target gene prediction and pathway analysis showed the involvement of miR-100, miR-222, and miR-30a in pathways implicated in cancer pathogenesis, membrane vesiculation and therapy failure. Furthermore, D/exo co-culture assays and miRNA mimics transfection experiments indicated that miR-222-rich D/exo could alter target gene expression in MCF-7/S. Our results suggest that drug-resistant breast cancer cells may spread resistance capacity to sensitive ones by releasing exosomes and that such effects could be partly attributed to the intercellular transfer of specific miRNAs.

Resistance to chemotherapy and endocrine therapy as well as targeted drugs is a major problem in treatment of breast cancer. Over the last decades, emerging studies have revealed that extracellular vesicles, which are chronically released by breast cancer cells and surrounding stromal cells, influence the action of most commonly used therapeutics. Such modulatory effects have been related to the transport of biologically active molecules including proteins and functional microRNAs. In this review, we highlight recent studies regarding extracellular vesicle-mediated microRNA delivery in formatting drug resistance. We also suggest the use of extracellular vesicles as a promising method in antiresistance treatment.

Adriamycin (ADR) is an important chemotherapeutic agent frequently used in treatment of breast cancer. However, resistance to ADR results in treatment failure in many patients. Recent studies have indicated that microRNAs (miRNAs) may play an important role in such drug-resistance. In the present study, microRNA-452 (miR-452) was found to be significantly down-regulated in adriamycin-resistant MCF-7 cells (MCF-7/ADR) compared with the parental MCF-7 cells by miRNA microarray and real-time quantitative PCR (RT-qPCR). MiR-452 mimics and inhibitors partially changed the adriamycin-resistance of breast cancer cells, as also confirmed by apoptosis assay. In exploring the potential mechanisms of miR-452 in the adriamycin-resistance of breast cancer cells, bioinformatics analysis, RT-qPCR and Western blotting showed that dysregulation of miR-452 played an important role in the acquired adriamycin-resistance of breast cancer, maybe at least in part via targeting insulin-like growth factor-1 receptor (IGF-1R).

Objective: A chronic arteriovenous malformation (AVM) model using the swine retia mirabilia (RMB) was developed and compared with the human extracranial AVM (EAVM) both in hemodynamics and pathology, to see if this brain AVM model can be used as an EAVM model., Methods: We created an arteriovenous fistula between the common carotid artery and the external jugular vein in eight animals by using end-to-end anastomosis. All animals were sacrificed 1 month after surgery, and the bilateral retia were obtained at autopsy and performed hematoxylin and eosin staining and immunohistochemistry. Pre- and postsurgical hemodynamic evaluations also were conducted. Then, the blood flow and histological changes of the animal model were compared with human EAVM., Results: The angiography after operation showed that the blood flow, like human EAVM, flowed from the feeding artery, via the nidus, drained to the draining vein. Microscopic examination showed dilated lumina and disrupted internal elastic lamina in both RMB of model and nidus of human EAVM, but the thickness of vessel wall had significant difference. Immunohistochemical reactivity for smooth muscle actin, angiopoietin 1, and angiopoietin 2 were similar in chronic model nidus microvessels and human EAVM, whereas vascular endothelial growth factor was significant difference between human EAVM and RMB of model., Conclusions: The AVM model described here is similar to human EAVM in hemodynamics and immunohistochemical features, but there are still some differences in anatomy and pathogenetic mechanism. Further study is needed to evaluate the applicability and efficacy of this model.

Human parvovirus 4 (PARV4) is present in blood and blood products. As the presence and levels of PARV4 in Chinese source plasma pools have never been determined, we implemented real-time quantitative PCR to investigate the presence of PARV4 in source plasma pools in China. Results showed that 26·15% (51/195) of lots tested positive for PARV4. The amounts of DNA ranged from 2·83 × 10(3) copies/ml to 2·35×10(7) copies/ml plasma. The high level of PARV4 in plasma pools may pose a potential risk to recipients. Further studies on the pathogenesis of PARV4 are urgently required., (© 2012 The Author(s). Vox Sanguinis © 2012 International Society of Blood Transfusion.)

Objective: Infantile hemangiomas (IHs) on head and neck are frequently encountered. Recently, propranolol was introduced as a novel pharmacologic treatment for IH. But the impact of propranolol for the treatment of IHs especially the side effects have not yet been well described. This article aimed to describe the effects and side effects of propranolol treatment in 37 children with problematic hemangiomas on head and neck., Study Design: Data were collected from the medical charts of patients treated between October 2008 and November 2010. Serial examinations and photographs were obtained to evaluate perceived therapeutic response and complications of oral propranolol in the course of their therapy., Results: Thirty-seven infants with propranolol-treated problematic head and neck hemangiomas were included and all patients had a good response. Most of patients were subjectively noticed an obvious improvement within one week from the onset of therapy. 29 patients endured the treatment of propranolol for 3 months with no recurrence, 6 patients endured prolonged course of treatment for 5/6 months. 2 patients who endured the treatment of propranolol for 3 months were found recurrence in two weeks. So the propranolol was given again for another 3 months. There were no severe adverse reactions. Minor side effects included diarrhea, light sleeping, and nausea., Conclusion: Propranolol appears to be an effective and well-tolerated treatment for problematic IH on head and neck., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To summarize the CT and MRI features in a series of fifteen cases of Kimura's disease., Materials and Methods: The clinical data, CT and MRI findings of 15 patients with histologically proved Kimura's disease were retrospectively reviewed. All imaging data were consensually evaluated by two radiologists to determine the lesion location, number, morphology, margin, signal intensity or CT density, lesion texture, contrast enhancement pattern and involvement of adjacent structures., Results: There were 14 male and 1 female, with peripheral blood eosinophilia in all 14 patients. 13 patients were presented with a painless mass. 13 patients had lesions located in the head and neck related to the major salivary glands. 1 patient had lesion in groin. Subcutaneous fat diffuse atrophy around the tumor site was found in 11 patients. 9 patients had solitary mass and 6 patients had multiple masses. Most masses were ill-defined, but no specific density or signal patterns were found. Most patients exhibited enlarged or obviously enhanced abnormal lymph nodes but without necrosis., Conclusion: The characteristic distribution, morphology with enlarged draining lymphadenopathy, combined with the clinical features and laboratory examination enables a confident preoperative diagnosis of Kimura's disease., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and "NO-Astrocyte-Cytokine-NMDAR-Neuron" pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN.