Extracellular Vesicles Derived from Bone Mesenchymal Stem Cells Carrying circ_0000075 Relieves Cerebral Ischemic Injury by Competitively Inhibiting miR-218-5p and Up-regulating E3 Ubiquitin Ligase SMURF2.

Extracellular vesicle (EV)-encapsulated circRNAs have the potential role in affecting brain disorders. However, the role of circ_0000075 in cerebral ischemic injury remains unclear. Here, we tried to investigate the mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs carrying circ_0000075 in the control of cerebral ischemic injury. Initially, a mouse model with cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO), followed by the determination of circ_0000075 expression. Then, neurons were isolated and subjected to oxygen-glucose deprivation/reperfusion. BMSCs were isolated for extraction of EVs. The correlation among circ_0000075, microRNA (miR)-218-5p, and Smad ubiquitination regulatory factor 2 (SMURF2) was detected with their roles in cerebral ischemic injury analyzed in vivo and in vitro. circ_0000075 was down-regulated in MCAO mice and engineered RVG-EVs were internalized by neurons to up-regulate circ_0000075 expression. Treatment of RVG-circ_0000075-EVs reduced brain tissue damage, increased neuronal count, and significantly curtailed apoptosis rate, suppressing cerebral ischemic injury in vitro and in vivo. miR-218-5p was targeted by circ_0000075 in neurons, which promoted SMURF2 expression. A negative correlation between SMURF2 and transcriptional regulator Yin Yang 1 (YY1) was identified. In vitro experiments further proved that circ_ 00,000 75 could down-regulate the expression of YY1 through SMURF2, and finally relieving cerebral ischemic injury. Collectively, engineered EVs delivered circ_0000075 into brain tissues and increased circ_0000075 expression, which down-regulated miR-218-5p and up-regulated SMURF2, thus alleviating cerebral ischemic injury.

Induction of cancer cell stemness in glioma through glycolysis and the long noncoding RNA HULC-activated FOXM1/AGR2/HIF-1α axis.

Gliomas are the most common primary intracranial tumor, accounting for more than 70% of brain malignancies. Studies indicate that highly upregulated in liver cancer (HULC), a long noncoding RNA (lncRNA), functions as an oncogene in gliomas. However, the underlying mechanism of HULC in gliomas remains under-studied and was subsequently investigated in the current study. Brain tissues were clinically collected from 50 patients with glioblastoma (GBM) and 35 patients with acute craniocerebral injury, followed by immunohistochemical detection of the expression patterns of Forkhead box M1 (FOXM1), anterior gradient 2 (AGR2), and hypoxia-inducible factor-1α (HIF-1α). After flow cytometry-based sorting of the CD133+ glioma stem cells (GSCs) from the U251 cell line, the obtained cells were subjected to lentivirus infection. Afterwards, the proliferation, stemness, and apoptosis of GSCs were evaluated using sphere formation, immunofluorescence, and flow cytometry assays, respectively. In addition, the interactions among HULC, FOXM1, AGR2, and HIF-1α were identified using RNA immunoprecipitation (RIP), RNA pull-down, Chromatin immunoprecipitation (ChIP), IP, and dual luciferase reporter assays. Last, the specific effects were validated in vivo. HULC was upregulated in GBM tissues and GSCs, which may promote the progression of glioma. On the other hand, silencing of HULC reduced the stemness, inhibited the proliferation, and promoted the apoptosis and differentiation of GSCs. In addition, HULC further stabilized FOXM1 expression in GSCs through ubiquitination, while FOXM1 activated AGR2 transcription to promote HIF-1α expression. Moreover, HULC promoted the glycolysis and stemness of GSCs through its regulation of the FOXM1/AGR2/HIF-1α axis, consequently exacerbating the occurrence and development of glioma. The findings obtained in our study indicate that HULC stabilizes the FOXM1 protein by ubiquitination to upregulate the expression of AGR2 and HIF-1α, which further promote the glycolysis of and maintain the stemness of GSCs, to enhance the tumorigenicity of GSCs, highlighting a novel therapeutic target for glioma.

Extracellular vesicles derived from M2 microglia reduce ischemic brain injury through microRNA-135a-5p/TXNIP/NLRP3 axis.

Accumulating evidences have suggested that extracellular vesicles (EVs) are crucial players in the pathogenesis of ischemic brain injury. This study was designed to explore the specific functions of M2 phenotype microglia-derived EVs in ischemic brain injury progression. The expression of microRNA-135a-5p (miR-135a-5p) in M2 microglia-derived EVs was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by the identification of expression relationship among miR-135a-5p, thioredoxin-interacting protein (TXNIP), and nod-like receptor protein 3 (NLRP3) by dual luciferase reporter gene assay. After construction of an oxygen-glucose deprivation/reperfusion (OGD/R) cell model, the effects of miR-135a-5p on the biological characteristics of HT-22 cells were assessed by cell counting kit 8 (CCK-8) assay and flow cytometry. Finally, a mouse model of transient middle cerebral artery occlusion (tMCAO) was established and cerebral infarction volume was determined by triphenyltetrazolium chloride (TTC) staining and the expression of IL-18 and IL-1ß in the brain tissue was determined by enzyme-linked immunosorbent assay (ELISA). We found that M2 microglia-derived EVs had high expression of miR-135a-5p, and that miR-135a-5p in M2 microglia-derived EVs negatively regulated the expression of NLRP3 via TXNIP. Overexpression of miR-135a-5p promoted the proliferation but inhibited the apoptosis of neuronal cells, and inhibited the expression of autophagy-related proteins. M2 microglia-derived EVs delivered miR-135a-5p into neuronal cells to inhibit TXNIP expression, which further inhibited the activation of NLRP3 inflammasome, thereby reducing neuronal autophagy and ischemic brain injury. Hence, M2 microglia-derived EVs are novel therapeutic targets for ischemic brain injury treatment.

[Clinical features of coronavirus disease 2019 in children: a systemic review of severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019].

OBJECTIVE: To systematically summarize the clinical features of coronavirus disease 2019 (COVID-19) in children. METHODS: PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Weipu Database, and Wanfang Database were searched for clinical studies on COVID-19 in children published up to May 21, 2020. Two reviewers independently screened the articles, extracted data, and assessed the risk of bias of the studies included. A descriptive analysis was then performed for the studies. Related indices between children with COVID-19 and severe acute respiratory syndromes (SARS) or Middle East respiratory syndrome (MERS) were compared. RESULTS: A total of 75 studies were included, with a total of 806 children with COVID-19. The research results showed that the age of the children ranged from 36 hours after birth to 18 years, with a male-female ratio of 1.21 : 1. Similar to SARS and MERS, COVID-19 often occurred with familial aggregation, and such cases accounted for 74.6% (601/806). The children with COVID-19, SARS, and MERS had similar clinical symptoms, mainly fever and cough. Some children had gastrointestinal symptoms. The children with asymptomatic infection accounted for 17.9% (144/806) of COVID-19 cases, 2.5% (2/81) of SARS cases, and 57.1% (12/21) of MERS cases. The children with COVID-19 and MERS mainly had bilateral lesions on chest imaging examination, with a positive rate of lesions of 63.4% (421/664) and 26.3% (5/19) respectively, which were lower than the corresponding positive rates of viral nucleic acid detection, which were 99.8% and 100% respectively. The chest radiological examination of the children with SARS mainly showed unilateral lesion, with a positive rate of imaging of 88.9% (72/81), which was higher than the corresponding positive rate of viral nucleic acid detection (29.2%). Viral nucleic acid was detected in the feces of children with COVID-19 or SARS, with positive rates of 60.2% (56/93) and 71.4% (5/7) respectively. The children with COVID-19 had a rate of severe disease of 4.6% (31/686) and a mortality rate of 0.1% (1/806), the children with SARS had a rate of severe disease of 1.5% (1/68) and a mortality rate of 0%, and those with MERS had a rate of severe disease of 14.3% (3/21) and a mortality rate of 9.5% (2/21). CONCLUSIONS: Children with COVID-19 have similar symptoms to those with SARS or MERS, mainly fever and cough. Asymptomatic infection is observed in all three diseases. Children with COVID-19 or SARS have milder disease conditions than those with MERS. COVID-19 in children often occurs with familial aggregation. Epidemiological contact history, imaging examination findings, and viral nucleic acid testing results are important bases for the diagnosis of COVID-19.

Human marrow stromal cells secrete microRNA-375-containing exosomes to regulate glioma progression.

It is well established that human marrow stromal cells (hMSCs) can directly migrate towards tumor microenvironments associated with tumor formation and intracellular communication. Gene regulatory networks in tumors may be targeted by microRNAs (miRNAs), especially those derived in exosomes from hMSCs. However, the potential functional roles of hMSCs in glioma cell growth still remain controversial. Therefore, this study aimed at exploring the regulatory mechanisms of hMSC exosomal microRNA-375 (miR-375) in glioma. Microarray analysis was used to initially screen out glioma-related genes. The interaction between miR-375 and solute carrier family 31 member 1 (SLC31A1) was confirmed by dual-luciferase reporter gene assay. miR-375 and SLC31A1 expression in glioma cells were determined. Glioma cells were initially exposed to exosomes derived from hMSCs treated with miR-375. Subsequently, the rates of proliferation, migration, invasion and apoptosis were determined in glioma cells using in vitro assays. The effects of exosomal miR-375 from hMSCs on tumor growth in vivo were also measured using xenograft tumor in nude mice. We found that miR-375 and SLC31A1 showed significantly lower and higher expression of glioma cells respectively. Additionally, restored miR-375 expression resulted in suppressed cell proliferation, migration and invasion, and increased apoptosis by targeting SLC31A1. Next, in vitro experiments demonstrated that hMSC-derived exosomes overexpressing miR-375 promoted apoptosis while suppressing proliferation, migration and invasion. Furthermore, in vivo experiments confirmed the negative regulatory effects of hMSC-derived exosomes with overexpressed miR-375. We conclude that exosomal miR-375 from hMSCs inhibits glioma cell progression through SLC31A1 suppression, and ultimately serves as a potential target in the treatment of gliomas.

[Expression and Significance of HIF-3α in Mitochondria].

OBJECTIVE: To investigate the mitochondrial translocation of hypoxia inducible factor-3α (HIF-3α) under normoxia and hypoxia and its physiological and pathological meanings. METHODS: ① After hypoxic (1%O2) or DMOG, CoCl2 treatments mimicking the hypoxic treatment, Western blot and immunofluorescence were used to examine the HIF-3α expression in mitochondria of HeLa and ACHN cells, respectively. ②The protease sensitivity experiment was used to explore the sub-organelle localization of HIF-3α in mitochondria. ③Western blot was used to examine mitochondrial HIF-3α in the normal mouse tissues and human liver carcinoma tissues. RESULTS: ① In HeLa and ACHN cells, HIF-3α translocated to mitochondria under normoxia and hypoxia, and its mitochondrial expression was higher under hypoxia; ②The protease sensitivity of HIF-3α was similar to proteins locating in the mitochondrial outer membrane; ③Mitochondrial HIF-3α expressed in multiple normal mouse tissues; The expression of mitochondrial HIF-3α was higher in human liver carcinoma tissues than the normal and adjacent tissues. CONCLUSIONS: HIF-3α translocated to mitochondrial outer membrane under both normoxia and hypoxia, and hypoxia could up-regulated HIF-3α mitochondrial translocation. Meanwhile, the phenomenon may be involved in the process of liver carcinoma.

[MHC-I epitope presentation prediction based on transfer learning].

Accurate epitope presentation prediction is a key procedure in tumour immunotherapies based on neoantigen for targeting T cell specific epitopes. Epitopes identified by mass spectrometry (MS) is valuable to train an epitope presentation prediction model. In spite of the accelerating accumulation of MS data, the number of epitopes that match most of human leukocyte antigens (HLAs) is relatively small, which makes it difficult to build a reliable prediction model. Therefore, this research attempted to use the transfer learning method to train a model to learn common features among the mixed allele specific epitopes. Then based on this pre-trained model, we used the allele-specific epitopes to train the final epitope presentation prediction model, termed Pluto. The average 0.1% positive predictive value (PPV) of Pluto outperformed the prediction model without pretraining with a margin of 0.078 on the same validation dataset. When evaluating Pluto on external HLA eluted ligand datasets, Pluto achieved an averaged 0.1% PPV of 0.4255, which is better than the prediction model without pretraining (0.3824) and other popular methods, including MixMHCpred (0.3369), NetMHCpan4.0-EL (0.4000), NetMHCpan4.0-BA (0.3188) and MHCflurry (0.3002). Moreover, when it comes to the evaluation of predicting immunogenicity, Pluto can identify more neoantigens than other tools. Pluto is publicly available at https://github.com/weipenegHU/Pluto.

[Involvement of intrathecal activation of MrgC receptor in pathological pain and morphine tolerance].

Rodent MrgC receptor (Mas-related G-protein-coupled receptor subtype C) shares 65% sequence homology and similarities in terms of expression pattern and binding profile with human Mas-related gene X receptor 1 (hMrgX1). Therefore, researchers generally explore the role of hMrgX1 by studying the function of MrgC receptor. Murine MrgC receptor is uniquely expressed in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia (TG), which is closely related to the transmission process of pain. This review summarizes the analgesic effects of intrathecal activation of MrgC receptors in pathological pain and morphine tolerance.

Down-regulated microRNA-30b-3p inhibits proliferation, invasion and migration of glioma cells via inactivation of the AKT signaling pathway by up-regulating RECK.

microRNAs (miRNAs) have been found to affect various cancers, and expression of numerous miRNAs is revealed in glioma. However, the role of microRNA-30b-3p (miR-30b-3p) in glioma remains elusive. Therefore, the present study aims to explore the specific mechanism by which miR-30b-3p influence the development of glioma in relation to the AKT signaling pathway. First, glioma cell lines were collected with miR-30b-3p and reversion-inducing cysteine-rich protein with kazal motifs (RECK) expression measured. The functional role of miR-30b-3p and RECK in glioma was determined via gain- and loss-of-function approaches. Subsequently, the expression of invasion- and migration-related factors (MMP-2 and MMP-9) and the AKT signaling pathway-related factors (AKT, p-AKT and PI3K-p85) was detected. Moreover, in vivo experiments were also conducted to investigate how miR-30b-3p influences in vivo tumorigenesis. The results showed that miR-30b-3p was up-regulated and RECK was down-regulated in glioma. RECK was a target gene of miR-30b-3p. Decreased miR-30b-3p and overexpressed RECK led to decreased expression of MMP-2, MMP-9 and p-AKT. Overexpressed RECK and LY294002 could decrease p-AKT and PI3K-p85 expression accompanied with unchanged expression of total protein of AKT. Additionally, proliferation, migration and invasion of glioma cells and tumor formation in nude mice were repressed owing to reduced expression of miR-30b-3p or elevated expression of RECK. In summary, miR-30b-3p inhibition suppresses metastasis of glioma cells by inactivating the AKT signaling pathway via RECK up-regulation, providing a new target for glioma treatment.

Silencing microRNA-221/222 cluster suppresses glioblastoma angiogenesis by suppressor of cytokine signaling-3-dependent JAK/STAT pathway.

Angiogenesis is a major pathologic characteristic of glioblastoma, which is one aggressive primary brain tumor. MicroRNA-221/222 (miR-221/222) cluster has been previously reported to function importantly in malignant glioma biological process. The current study aims at evaluating the effects of miR-221/222 cluster on angiogenesis of glioblastoma cells. Microarray data were analyzed to select glioblastoma-associated differentially expressed genes, and dual-luciferase reporter assay was performed to assess targeting correlation between miR-221/222 cluster and suppressor of cytokine signaling-3 (SOCS3). Subsequently, the expression patterns of miR-221 and miR-222 in glioblastoma cells were identified. miR-221 and miR-222 were overexpressed or silenced in glioblastoma cells to identify the effect of miR-221/222 cluster in cell invasion, migration, proliferation, and angiogenesis. To define downstream pathway of miR-221/222 cluster or SOCS3 in glioblastoma, levels of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway-related proteins were assessed. Additionally, the functions of miR-221/222 on glioblastoma cell angiogenesis were measured in vivo with microvessel density assayed. miR-221 and miR-222 were expressed at a high level and SOCS3 was at a low level in glioblastoma. Downregulation of the miR-221/222 cluster diminished the invasion, migration, proliferation, and angiogenesis with reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, and vascular endothelial growth factor in glioblastoma cells. Also, silencing miR-221/222 cluster reduced p-JAK2/JAK2 and p-STAT3/STAT3. Consistently, the inhibitory role of silencing miR-221/222 cluster on tumorigenesis of glioblastoma cells was confirmed in vivo. Collectively, the inhibition of miR-221/222 cluster could attenuate the glioblastoma angiogenesis through inactivation of the JAK/STAT pathway by upregulating SOCS3.

HIF-1α protects against oxidative stress by directly targeting mitochondria.

The transcription factor hypoxia inducible factor-1α (HIF-1α) mediates adaptive responses to oxidative stress by nuclear translocation and regulation of gene expression. Mitochondrial changes are critical for the adaptive response to oxidative stress. However, the transcriptional and non-transcriptional mechanisms by which HIF-1α regulates mitochondria in response to oxidative stress are poorly understood. Here, we examined the subcellular localization of HIF-1α in human cells and identified a small fraction of HIF-1α that translocated to the mitochondria after exposure to hypoxia or H2O2 treatment. Moreover, the livers of mice with CCl4-induced fibrosis showed a progressive increase in HIF-1α association with the mitochondria, indicating the clinical relevance of this finding. To probe the function of this HIF-1α population, we ectopically expressed a mitochondrial-targeted form of HIF-1α (mito-HIF-1α). Expression of mito-HIF-1α was sufficient to attenuate apoptosis induced by exposure to hypoxia or H2O2-induced oxidative stress. Moreover, mito-HIF-1α expression reduced the production of reactive oxygen species, the collapse of mitochondrial membrane potential, and the expression of mitochondrial DNA-encoded mRNA in response to hypoxia or H2O2 treatment independently of nuclear pathways. These data suggested that mitochondrial HIF-1α protects against oxidative stress induced-apoptosis independently of its well-known role as a transcription factor.

Standard Protocol Items for Clinical Trials with Traditional Chinese Medicine 2018: Recommendations, Explanation and Elaboration (SPIRIT-TCM Extension 2018).

Traditional Chinese Medicine (TCM) is one of the oldest systems of medicine. More and more attention has been paid to TCM application, but the variable quality of clinical trials with TCM impedes its widespread acceptance. The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement has established guidelines for designing clinical trials to ensure that the trial results are accurate and reliable. However, there are difficulties when applying SPIRIT 2013 Statement to trials with TCM, due to the unique theory and the characteristic of TCM intervention. An Extension to the original SPIRIT was developed to ensure the quality of trial design with TCM. As Chinese herbal formulae, acupuncture and moxibustion are common and representative interventions in TCM practice, the executive working group determined that the SPIRIT-TCM Extension focus on these three interventions. Extension was developed through initiation, 3 rounds of Delphi consensus survey, and finalizing expert meeting. Seven items from the SPIRIT 2013 Statement were modified, namely, "title", "background and rationale", "objectives", "eligibility criteria", "interventions", "outcomes", and "data collection methods". The Extension includes the introduction of the concept of TCM pattern and 3 major TCM interventions, with examples and explanations. The SPIRIT-TCM Extension 2018 provides suggestion for investigators in designing high quality TCM clinical trials. It is expected that wide dissemination and application of this extension ensure continuous improvement of TCM trial quality throughout the world.

The Effect of Acupuncture on the Quality of Life in Patients With Migraine: A Systematic Review and Meta-Analysis.

Background: Acupuncture is frequently used as an efficient method to prevent and treat migraines. However, its effect on the quality of life remains controversial. Methods: Seven databases, such as PubMed and Cochrane Library were searched to retrieve reference lists of eligible trials and related reviews. Randomized controlled trials that were published in Chinese and English were included. Results: Acupuncture resulted in lower Visual Analog Scale scores than the medication group at 1 month after treatment (MD -1.22, 95%CI -1.57 to -0.87; low quality) and 1-3 months after treatment (MD -1.81, 95%CI -3.42 to -0.20; low quality). Compared with sham acupuncture, acupuncture resulted in lower Visual Analog Scale scores at 1 month after treatment (MD -1.56, 95%CI -2.21 to -0.92; low quality). Conclusion: Acupuncture exhibits certain efficacy both in the treatment and prevention of migraines, which is superior to no treatment, sham acupuncture and medication. Further, acupuncture enhanced the quality of life more than did medication.

Application of fluorescein sodium in breast cancer brain-metastasis surgery.

OBJECTIVE: Surgical resection serves an important role in the multidisciplinary treatment of cerebral metastases (CMs). Conventional white-light, microsurgical, and circumferential stripping of CMs is standard neurosurgical procedure, but is associated with a high recurrence rate. Based on this outcome, there is an urgent need for a new surgical strategy, such as fluorescence-guided resection, for CMs, in order to achieve total removal. METHODS: A retrospective study was carried out in 38 patients clinically and pathologically diagnosed with breast cancer brain metastasis at three medical centers from May 2012 to June 2016. The study comprised group 1 (fluorescein-guided surgery) and group 2 (standard microsurgery). In group 1, 5 mg/kg of fluorescein sodium was injected intravenously after an allergy test and before general anesthesia for 17 patients. A yellow 560 filter was employed for microsurgical tumor resection. Group 2 consisted of 21 patients for whom fluorescein was not administered. RESULTS: Surgical outcomes were assessed concerning the extent of resection and Karnofsky performance status. Gross total resection was achieved in these patients, with high fluorescence markedly enhancing tumor visibility. The extent of resection had a powerful influence on performance status. Overall survival after CM was 24.1 months in patients given fluorescein and was 22.8 months in the nonfluorescein group. CONCLUSION: Fluorescein-guided surgery is a simple, safe, and practical method to resect breast cancer brain metastasis, and leads to a higher proportion of resection compared to common microsurgery. This offers a tremendous advantage when navigating a tiny tumor, and improves the quality of life of patients with CM.

Effect of Regulatory Network of Exosomes and microRNAs on Neurodegenerative Diseases.

OBJECTIVE: A comprehensive review of the network regulation of exosomes and microRNAs (miRNAs) in neurodegenerative diseases was done, centering on the mechanism of the formation of exosomes and miRNAs and the sorting mechanism of exosomal miRNAs, with the aim to provide a theoretical basis in the search of biomarkers and the treatment of neurodegenerative diseases. DATA SOURCES: The comprehensive search used online literature databases including NCBI PubMed, Web of Science, Google Scholar, and Baidu Scholar. STUDY SELECTION: The study selection was based on the following keywords: exosomes, miRNAs, central nervous system (CNS), and neurodegenerative diseases. The time limit for literature retrieval was from the year 2000 to 2018, with language restriction in English. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type. RESULTS: Exosomes are the smallest nanoscale membranous microvesicles secreted by cells and contain important miRNAs, among other rich contents. In the CNS, exosomes can transport amyloid ß-protein, α-synuclein, Huntington-associated protein 1, and superoxide dismutase I to other cells. These events relieve the abnormal accumulation of proteins and aggravating neurological diseases. In some neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, miRNAs are pathologically altered as an inexorable course, suggesting that miRNAs may contribute neurodegeneration. Exosomes and miRNAs form a network to regulate the homeostasis of the CNS, both synergistically and individually. CONCLUSION: The network of exosomes and miRNAs that regulates CNS homeostasis is a promising biomarker for the diagnosis and treatment of neurodegenerative diseases.

[Pollution Characteristics and Health Risk Assessment of Atmospheric VOCs in Chengdu].

Volatile organic compounds (VOCs) were measured in atmospheric samples collected from urban and roadside atmospheric environments in Chengdu in September 2012. The composition, chemical reactivity, and concentration level and its variation characteristics of VOCs were studied, and the health risk of aromatic compounds was assessed. Results showed that the mean mass concentrations of total VOCs (TVOCs) were (108.57±52.43) µg·m-3 and (132.61±49.31) µg·m-3 for the urban and roadside atmospheric environments, respectively. The highest mass concentrations were observed for alkanes, followed by aromatics, alkenes, and alkynes. Aromatics and alkenes contributed more to ozone formation potential (OFP) of the urban and roadside atmospheric environments, and m/p-xylene, toluene, ethene, o-xylene, and propene were the key reactive species. The values of hazard quotient and hazard index were less than 1 for benzene, toluene, ethylbenzene, and o-xylene (BTEX), showing that they had no appreciable risk of non-cancer health effects on the exposed population. However, the value of cancer risk was above the safety threshold for benzene, showing that it was a potential cancer risk to the exposed population.

[Evidence-based Chinese medicine：theory and practice].

The introduction and popularization of evidence-based medicine has opened up a new research field of clinical efficacy evaluation of traditional Chinese medicine(TCM), produced new research ideas and methods, and promoted the progress of clinical research of TCM. After about 20 years assiduous study and earnest practice, the evidence based evaluation method and technique, which conforms to the characteristics of TCM theory and practice, has been developing continuously. Evidence-based Chinese medicine (EBCM) has gradually formed and become an important branch of evidence-based medicine. The basic concept of evidence-based Chinese medicine: EBCM is an applied discipline, following the theory and methodology of evidence-based medicine, to collect, evaluate, produce, transform the evidence of effectiveness, safety and economy of TCM, to reveal the feature and regular pattern of TCM taking effect, and to guide the development of clinical guidelines, clinical pathways and health decisions. The effects and achievements of EBCM development: secondary studies mainly based on systematic review/Meta-analysis were extensively carried out; clinical efficacy studies mainly relying on randomized controlled trials grew rapidly; clinical safety evaluations based on real world study have been conducted; methodological researches mainly focused on study quality control deepened gradually; internationalization researches mainly on report specifications have got some breakthroughs; standardization researches based on treatment specification were strengthened gradually; the research team and talents with the characteristics of inter-disciplinary have been steadily increased. A number of high-quality research findings have been published at international well-known journals; the clinical efficacy and safety evidence of TCM has been increased; the level of clinical rational use of TCM has been improved; a large number of Chinese patent medicines with big market have been cultured. The future missions of EBCM mainly consist of four categories (scientific research, methodology and standard, platform construction and personnel training) with nine tasks. ①Carry out systematic reviews to systematically collect clinical trial reports of TCM and establish database of clinical evidence of TCM; ②Carry out evidence transformation research to lay the foundation for the development of clinical diagnosis and treatment guidelines, clinical pathways of TCM, and for the screening of basic drug list and medical insurance list, and for the policy-making relevant to TCM; ③Conduct researches to evaluate the advantages and effective regular patterns of TCM and form the evidence chain of TCM efficacy; ④Carry out researches for the safety evaluation of TCM, and provide evidence supporting the rational and safe use of TCM in clinical practice; ⑤Conduct researches on methodology of EBCM and provide method for developing high quality evidence; ⑥Carry out researches to develop standards and norms of TCM, and to form methods, standards, specifications and technical systems; ⑦Establish data management platform for evidence-based evaluation of TCM, and promote data sharing; ⑧Build international academic exchange platform to promote international cooperation and mutual recognition of EBCM research; ⑨Carry out education and popularization activities of evidence-based evaluation methods, and train undergraduate students, graduate students, clinical healthcare providers and practitioners of TCM. The development of EBCM, as it was, not only promoted the transformation of clinical research and decision-making mode of TCM, contributed to the modernization and internationalization of TCM, but also enriched the connotation of Evidence-based Medicine.

Prognostic factors for olfactory groove meningioma with nasal cavity extension.

OBJECTIVES: Meningioma recurrence remains a significant issue. No study has described the relationship between the clinical features and prognosis of communicating meningioma that primarily originates from the olfactory groove. The aim of the study was to identify prognostic factors of communicating olfactory groove meningiomas that could be stratified according to their risk of recurrence. RESULTS: A Simpson grade one or two resection was achieved. Complications with cerebrospinal rhinorrhoea occurred in two patients: one required reoperation, and the other was managed successfully with external drainage of lumbar cistern. There were 5 known clinical recurrences within the median follow-up of more than 5 years. The median 5-year recurrence-free survival for patients was 88.4%. Factors such as gender, tumour size, T2 signal and the hyperostotic bone had no significant effect on recurrence-free survival. However, recurrence was activated by oedema range, hyperostosis, dural tail sign and tumor texture (p < 0.05). Interestingly, female patients with the disease were younger than males at diagnosis, and the difference was statistically significant ( p = 0.013). CONCLUSIONS: Based on these features of communicating olfactory groove meningiomas, different strategies may be adopted for the follow-up and subsequent treatment. Due to the relatively uncommon incidence, more investigations into the clinical behaviour of this entity are crucial. PATIENTS AND METHODS: A retrospective study of 43 patients harbouring olfactory groove meningiomas invading the ethmoid or nasal cavity was conducted at three medical centers from 2000 to 2010. The records were reviewed for clinical presentations, imaging studies, surgical observation, histological features and follow-up.

Toward Evidence-Based Chinese Medicine: Status Quo, Opportunities and Challenges.

How to test the treatments of Chinese medicine (CM) and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM. For centuries, various approaches have been used to identify and measure the efficacy and safety of CM. However, the high-quality evidence related to CM that produced in China is still rare. Over the recent years, evidence-based medicine (EBM) has been increasingly applied to CM, strengthening its theoretical basis. This paper reviews the past and present state of CM, analyzes the status quo, challenges and opportunities of basic research, clinical trials, systematic reviews, clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China, pointing out how EBM can help to make CM more widely used and recognized worldwide.