Auditory training remodels hippocampus-related memory in adult rats.

Consequences of perceptual training, such as improvements in discriminative ability, are highly stimulus and task specific. Therefore, most studies on auditory training-induced plasticity in adult brain have focused on the sensory aspects, particularly on functional and structural effects in the auditory cortex. Auditory training often involves, other than auditory demands, significant cognitive components. Yet, how auditory training affects cognition-related brain regions, such as the hippocampus, remains unclear. Here, we found in female rats that auditory cue-based go/no-go training significantly improved the memory-guided behaviors associated with hippocampus. The long-term potentiations of the trained rats recorded in vivo in the hippocampus were also enhanced compared with the naïve rats. In parallel, the phosphorylation level of calcium/calmodulin-dependent protein kinase II and the expression of parvalbumin-positive interneurons in the hippocampus were both upregulated. These findings demonstrate that auditory training substantially remodels the processing and function of brain regions beyond the auditory system, which are associated with task demands.

Genetically encoded bioorthogonal tryptophan decaging in living cells.

Tryptophan (Trp) plays a critical role in the regulation of protein structure, interactions and functions through its π system and indole N-H group. A generalizable method for blocking and rescuing Trp interactions would enable the gain-of-function manipulation of various Trp-containing proteins in vivo, but generating such a platform remains challenging. Here we develop a genetically encoded N1-vinyl-caged Trp capable of rapid and bioorthogonal decaging through an optimized inverse electron-demand Diels-Alder reaction, allowing site-specific activation of Trp on a protein of interest in living cells. This chemical activation of a genetically encoded caged-tryptophan (Trp-CAGE) strategy enables precise activation of the Trp of interest underlying diverse important molecular interactions. We demonstrate the utility of Trp-CAGE across various protein families, such as catalase-peroxidases and kinases, as translation initiators and posttranslational modification readers, allowing the modulation of epigenetic signalling in a temporally controlled manner. Coupled with computer-aided prediction, our strategy paves the way for bioorthogonal Trp activation on more than 28,000 candidate proteins within their native cellular settings.

Reduced atmospheric sulfate enhances fine particulate nitrate formation in eastern China.

Nitrate (NO3-) is a major component of atmospheric fine particles. Recent studies in eastern China have shown the increasing trend of NO3- in contrast to the ongoing control of nitrogen oxide (NOx). Here, we elucidate the effects of reduced sulfur dioxide (SO2) on the enhancement of NO3- formation based on field measurements at the summit of Mt. Tai (1534 m a.s.l.) and present detailed modelling analyses. From 2007 to 2018, the measured springtime concentrations of various primary pollutants and fine sulfate (SO42-) decreased sharply (-16.4 % to -89.7 %), whereas fine NO3- concentration increased by 22.8 %. The elevated NO3- levels cannot be explained by the changes in meteorological conditions or other related parameters but were primarily attributed to the considerable reduction in SO42- concentrations (-73.4 %). Results from a multi-phase chemical box model indicated that the reduced SO42- levels decreased the aerosol acidity and prompted the partitioning of HNO3 into the aerosol phase. WRF-Chem model analyses suggest that such a negative effect is a regional phenomenon throughout the planetary boundary layer over eastern China in spring. This study provides new insights into the worsening situation of NO3- aerosol pollution and has important implications for controlling haze pollution in China.

Pairing with Enriched Sound Exposure Restores Auditory Processing Degraded by an Antidepressant.

Antidepressants, while effective in treating depression and anxiety disorders, also induce deficits in sensory (particularly auditory) processing, which in turn may exacerbate psychiatric symptoms. How antidepressants cause auditory signature deficits remains largely unknown. Here, we found that fluoxetine-treated adult female rats were significantly less accurate when performing a tone-frequency discrimination task compared with age-matched control rats. Their cortical neurons also responded less selectively to sound frequencies. The degraded behavioral and cortical processing was accompanied by decreased cortical perineuronal nets, particularly those wrapped around parvalbumin-expressing inhibitory interneurons. Furthermore, fluoxetine induced critical period-like plasticity in their already mature auditory cortices; therefore, a brief rearing of these drug-treated rats under an enriched acoustic environment renormalized auditory processing degraded by fluoxetine. The altered cortical expression of perineuronal nets was also reversed as a result of enriched sound exposure. These findings suggest that the adverse effects of antidepressants on auditory processing, possibly because of a reduction in intracortical inhibition, can be substantially alleviated by simply pairing drug treatment with passive, enriched sound exposure. They have important implications for understanding the neurobiological basis of antidepressant effects on hearing and for designing novel pharmacological treatment strategies for psychiatric disorders.SIGNIFICANCE STATEMENT Clinical experience suggests that antidepressants adversely affect sensory (particularly auditory) processing, which can exacerbate patients' psychiatric symptoms. Here, we show that the antidepressant fluoxetine reduces cortical inhibition in adult rats, leading to degraded behavioral and cortical spectral processing of sound. Importantly, fluoxetine induces a critical period-like state of plasticity in the mature cortex; therefore, a brief rearing under an enriched acoustic environment is sufficient to reverse the changes in auditory processing caused by the administration of fluoxetine. These results provide a putative neurobiological basis for the effects of antidepressants on hearing and indicate that antidepressant treatment combined with enriched sensory experiences could optimize clinical outcomes.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway / 中国天然药物

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

Developmental Exposure to Bisphenol a Degrades Auditory Cortical Processing in Rats.

Developmental exposure to bisphenol A (BPA), an endocrine-disrupting contaminant, impairs cognitive function in both animals and humans. However, whether BPA affects the development of primary sensory systems, which are the first to mature in the cortex, remains largely unclear. Using the rat as a model, we aimed to record the physiological and structural changes in the primary auditory cortex (A1) following lactational BPA exposure and their possible effects on behavioral outcomes. We found that BPA-exposed rats showed significant behavioral impairments when performing a sound temporal rate discrimination test. A significant alteration in spectral and temporal processing was also recorded in their A1, manifested as degraded frequency selectivity and diminished stimulus rate-following by neurons. These post-exposure effects were accompanied by changes in the density and maturity of dendritic spines in A1. Our findings demonstrated developmental impacts of BPA on auditory cortical processing and auditory-related discrimination, particularly in the temporal domain. Thus, the health implications for humans associated with early exposure to endocrine disruptors such as BPA merit more careful examination.

Particulate organic nitrates at Mount Tai in winter and spring: Variation characteristics and effects of mountain-valley breezes and elevated emission sources.

Particulate organic nitrates, among the major components of secondary organic aerosols and fine particles, play important roles in regional nitrogen cycle, ozone budget, and cloud condensation nuclei formation. However, the pollution characteristics of particulate organic nitrates at mountain areas and the effects of anthropogenic pollutant transport remain poorly understood. In this study, field sampling and measurements were conducted at a high-elevation mountain site over North China Plain in winter and spring. Total five kinds of particulate organic nitrates in fine particles were determined by ultra-high performance liquid chromatography-electrospray mass spectrometry. The average total concentrations of particulate organic nitrates were 330 ± 121 ng m-3 and 247 ± 63 ng m-3 in winter and spring. The monoterpene-derived organic nitrates were the dominant components in both seasons with their contribution higher than 70%, accounting for 1.2 ± 0.8% and 2.0 ± 1.0% in organic aerosols in winter and spring, respectively. The significantly higher levels of particulate organic nitrates in winter than spring was ascribed to the strong effects of mountain-valley breezes and coal combustion plumes. The increasing concentrations of NOx and particulate matters brought by the valley breeze at daytime facilitated the formation of MHN215, OAKN359, and OAHN361, while the rising SO2 abundance and the sulfate aerosols transported by elevated emission sources affected the formation of MDCN247 at nighttime.

Degraded cortical temporal processing in the valproic acid-induced rat model of autism.

Hearing disorders, such as abnormal speech perception, are frequently reported in individuals with autism. However, the mechanisms underlying these auditory-associated signature deficits in autism remain largely unknown. In this study, we documented significant behavioral impairments in the sound temporal rate discrimination task for rats prenatally exposed to valproic acid (VPA), a well-validated animal model for studying the pathology of autism. In parallel, there was a large-scale degradation in temporal information-processing in their primary auditory cortices (A1) at both levels of spiking outputs and synaptic inputs. Substantially increased spine density of excitatory neurons and decreased numbers of parvalbumin- and somatostatin-labeled inhibitory inter-neurons were also recorded in the A1 after VPA exposure. Given the fact that cortical temporal processing of sound is associated with speech perception in humans, these results in the animal model of VPA exposure provide insight into a possible neurological mechanism underlying auditory and language-related deficits in individuals with autism.

Translation and validation of Chinese version of sense of competence in dementia care staff scale in healthcare providers: a cross-sectional study.

BACKGROUND: Healthcare providers' dementia-care competence is crucial for quality dementia care. A reliable and valid instrument is needed to assess the gaps in their dementia-care competence, and thereby identifying their educational needs. Therefore, this study aims to translate the 17-item Sense of Competence in Dementia Care Staff (SCIDS) scale into Chinese (SCIDS-C) and to validate the SCIDS-C among Chinese healthcare providers. METHODS: The translation procedure followed the modified Brislin's translation model. A cross-sectional survey was conducted using the translated version. The validity, including content validity, confirmatory factor analysis, concurrent validity and known-groups validity, was tested. Reliability in terms of internal consistency and test-retest reliability with a 2-week interval was evaluated. RESULTS: A total of 290 healthcare providers in 12 nursing homes and a hospital completed the survey. The scale-level content validity index was .99. The confirmatory factor analysis model marginally supported the original 4-factor structure. Positive but weak correlations were noted between the total score of the SCIDS-C and that of the Dementia Knowledge Assessment Scale (r = .17, p = .005) and Approaches to Dementia Questionnaire (r = .22, p < .001), suggesting acceptable concurrent validity. Differences between health professionals and care assistants were significant in two subscales scores. The internal consistency of the scale was high, with Cronbach's α of .87. Test-retest reliability was demonstrated with intra-class correlation coefficient of 0.88. CONCLUSIONS: The SCIDS-C demonstrated acceptable reliability and validity although the known-groups validity between health professionals and care assistants was not fully established. It can be used to measure the level of sense of competence and as an outcome measure in educational intervention aiming at improving dementia care among Chinese healthcare providers.

Validation of a Chinese version of the dementia knowledge assessment scale in healthcare providers in China.

AIMS: To translate 25-item Dementia Knowledge Assessment Scale into Chinese and evaluate its psychometric properties amongst Chinese healthcare providers. BACKGROUND: The prevalence of dementia is increasing in China, but development of relevant training for healthcare providers is still in its infancy stage. A comprehensive, valid and reliable Chinese knowledge-of-dementia measure is needed to identify training needs and evaluate the effect of educational interventions. DESIGN: A cross-sectional survey. METHODS: The Dementia Knowledge Assessment Scale was translated into Chinese following the modified Brislin's translation model. Content and face validity were established by an expert panel in dementia care and healthcare providers. A convenience sample of 290 healthcare providers in care homes and hospitals was recruited. Construct validity was evaluated through confirmatory factor analysis, concurrent validity and known groups' comparisons method. Reliability was evaluated through internal consistency reliability and 2-week test-retest reliability. This study used the STROBE checklist for reporting. RESULTS: The content validity index was 0.98. The confirmatory factor analysis model revealed that the four-factor model was partly supported in the present study. The moderate correlation between Chinese version of Dementia Knowledge Assessment Scale and Alzheimer's Disease Knowledge Scale indicated acceptable concurrent validity. The mean score of the scale and subscale scores showed significant differences between health professionals and care assistants, except for the subscale of "Care Considerations." The reliability was demonstrated with Cronbach's alpha of .77 and intra-class correlation coefficients of each subscale between .74 and .92 among 56 respondents. CONCLUSIONS: The Chinese version of Dementia Knowledge Assessment Scale demonstrated acceptable concurrent validity but marginal factorial validity and satisfactory reliability amongst Chinese healthcare providers. Therefore, applying the four-factor structure of Chinese version scale should be considered. RELEVANCE TO CLINICAL PRACTICE: Chinese version of Dementia Knowledge Assessment Scale can be used to understand the training needs of healthcare providers in dementia.

Longitudinal study on the trajectory and influencing factors of cancer-related fatigue in breast cancer patients during chemotherapy / 中国实用护理杂志

Objective:To investigate the longitudinal trajectory and influencing factors of cancer-related fatigue (CRF) in breast cancer patients during chemotherapy.Methods:From March 2019 to January 2020, breast cancer patients in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine and Peking Union Medical College Hospital were selected as the research objects to conduct follow-up investigation. The survey tools included general information questionnaire, Cancer-related Fatigue Assessment Scale, International Physical Activity Questionnaire, and the Pittsburgh Sleep Quality Index Scale.Results:A total of 91 patients were included in the study. The incidence of severe CRF at each time point before chemotherapy, 3 weeks after chemotherapy and 6 weeks after chemotherapy were 1.1% (1/91), 8.8% (5/57) and 2.1% (1/48), respectively. The results of the generalized estimation equation showed that the trajectory of the total score CRF firstly increased and then decreased, reaching a peak at 3 weeks after chemotherapy (35.45±13.07), and mild CRF change showed statistical difference ( P<0.05). In addition, BMI and sleep and daytime dysfunction were the influencing factors of the total score of CRF. Disease stage, sleep disturbance and daytime dysfunction were the influencing factors of CRF with different severity. Conclusions:CRF is a prominent problem in breast cancer patients during chemotherapy. Attention should be paid to high-risk individuals with abnormal BMI and daytime function by medical staff.

Environmental noise degrades hippocampus-related learning and memory.

The neural mechanisms underlying the impacts of noise on nonauditory function, particularly learning and memory, remain largely unknown. Here, we demonstrate that rats exposed postnatally (between postnatal days 9 and 56) to structured noise delivered at a sound pressure level of ∼65 dB displayed significantly degraded hippocampus-related learning and memory abilities. Noise exposure also suppressed the induction of hippocampal long-term potentiation (LTP). In parallel, the total or phosphorylated levels of certain LTP-related key signaling molecules in the synapses of the hippocampus were down-regulated. However, no significant changes in stress-related processes were found for the noise-exposed rats. These results in a rodent model indicate that even moderate-level noise with little effect on stress status can substantially impair hippocampus-related learning and memory by altering the plasticity of synaptic transmission. They support the importance of more thoroughly defining the unappreciated hazards of moderately loud noise in modern human environments.

Piezo1-Mediated Ca2+ Activities Regulate Brain Vascular Pathfinding during Development.

During development, endothelial tip cells (ETCs) located at the leading edge of growing vascular plexus guide angiogenic sprouts to target vessels, and thus, ETC pathfinding is fundamental for vascular pattern formation in organs, including the brain. However, mechanisms of ETC pathfinding remain largely unknown. Here, we report that Piezo1-mediated Ca2+ activities at primary branches of ETCs regulate branch dynamics to accomplish ETC pathfinding during zebrafish brain vascular development. ETC branches display spontaneous local Ca2+ transients, and high- and low-frequency Ca2+ transients cause branch retraction through calpain and branch extension through nitric oxide synthase, respectively. These Ca2+ transients are mainly mediated by Ca2+-permeable Piezo1 channels, which can be activated by mechanical force, and mutating piezo1 largely impairs ETC pathfinding and brain vascular patterning. These findings reveal that Piezo1 and downstream Ca2+ signaling act as molecular bases for ETC pathfinding and highlight a novel function of Piezo1 and Ca2+ in vascular development.

Novel Simultaneous Removal Technology of NO and SO2 Using a Semi-Dry Microwave Activation Persulfate System.

As it has a simple system and a small floor area, flue gas simultaneous desulfurization and denitrification technology has a good development prospect, and related research has become a hot topic in the field of flue gas purification. In this work, a novel simultaneous removal technology of NO and SO2 from flue gas using a semi-dry microwave activation persulfate system was developed for the first time. A series of experiments and characterization analyses had been implemented to research the feasibility of this new flue gas purification technology. The oxidation products, free radicals, and mechanism of NO and SO2 simultaneous removal were revealed. The effect of the main technological parameters on NO and SO2 simultaneous removal was also studied. Relevant results demonstrated that an increase in the microwave radiation power, persulfate concentration, and O2 concentration enhanced NO and SO2 simultaneous removal. The increase of NO and SO2 concentrations weakened NO and SO2 simultaneous removal. The reagent dosage, pH value of the solution, and reaction temperature showed a dual influence on NO and SO2 simultaneous removal. Free-radical capture experiments revealed that both SO4-• and •OH that were produced by microwave activation of persulfate were the major active species and played very key roles in NO and SO2 simultaneous removal. The main products (sulfate and nitrate) and byproducts (NO2) in the tail gas were found. The process application and product post-treatment routes were also proposed. The result may provide the necessary inspiration and guidance for the development and application of microwave-activated advanced oxidation technology in the flue gas treatment area.

Preparation of magnetic Co-Fe modified porous carbon from agricultural wastes by microwave and steam activation for mercury removal.

In this article, a magnetic cobalt-iron modified porous carbon derived from agricultural wastes by microwave and steam activation was developed to remove elemental mercury in coal-fired flue gas. The effects of operating parameters on Hg0 capture were discussed. Reaction mechanism and regeneration performance were also studied. Results show that the activation of microwave and steam significantly improves the pore structure of the porous carbon. The ultrasound-assisted impregnation promotes the dispersion of cobalt oxides and iron oxides on the samples. The Co0.4Fe12/RSWU(500) sorbent exhibits highest Hg0 removal efficiency at 130 °C. The characterization analysis shows that cobalt oxides and iron oxides are the main active components for Hg0 removal. The XPS analysis suggests that the chemisorption oxygen and the lattice oxygen (derived from Co3+/Co2+ and Fe3+/Fe2+) participate in the Hg0 capture process. Moreover, the cobalt-iron mixed oxide modified porous carbon has a good regeneration performance, which is conductive to reduce the costs in the future application.

Reversal of Age-Related Changes in Cortical Sound-Azimuth Selectivity with Training.

The compromised abilities to understand speech and localize sounds are two hallmark deficits in aged individuals. Earlier studies have shown that age-related deficits in cortical neural timing, which is clearly associated with speech perception, can be partially reversed with auditory training. However, whether training can reverse aged-related cortical changes in the domain of spatial processing has never been studied. In this study, we examined cortical spatial processing in ~21-month-old rats that were trained on a sound-azimuth discrimination task. We found that animals that experienced 1 month of training displayed sharper cortical sound-azimuth tuning when compared to the age-matched untrained controls. This training-induced remodeling in spatial tuning was paralleled by increases of cortical parvalbumin-labeled inhibitory interneurons. However, no measurable changes in cortical spatial processing were recorded in age-matched animals that were passively exposed to training sounds with no task demands. These results that demonstrate the effects of training on cortical spatial domain processing in the rodent model further support the notion that age-related changes in central neural process are, due to their plastic nature, reversible. Moreover, the results offer the encouraging possibility that behavioral training might be used to attenuate declines in auditory perception, which are commonly observed in older individuals.

One-step generation of zebrafish carrying a conditional knockout-knockin visible switch via CRISPR/Cas9-mediated intron targeting.

The zebrafish has become a popular vertebrate animal model in biomedical research. However, it is still challenging to make conditional gene knockout (CKO) models in zebrafish due to the low efficiency of homologous recombination (HR). Here we report an efficient non-HR-based method for generating zebrafish carrying a CKO and knockin (KI) switch (zCKOIS) coupled with dual-color fluorescent reporters. Using this strategy, we generated hey2zKOIS which served as a hey2 KI reporter with EGFP expression. Upon Cre induction in targeted cells, the hey2zCKOIS was switched to a non-functional CKO allele hey2zCKOIS-invassociated with TagRFP expression, enabling visualization of the CKO alleles. Thus, simplification of the design, and the visibility and combination of both CKO and KI alleles make our zCKOIS strategy an applicable CKO approach for zebrafish.

Long Non-Coding RNA HULC Enhances Tumor Growth in Orthotopic Xenograft Model of Glioblastoma / 中山大学学报(医学科学版)

@#【Objective】To investigate the mechanism of action of long non-coding RNA highly up-regulated in liver cancer（LncRNA HULC）on the growth of glioblastoma U87 cells in vitro and in vivo.【Methods】The cultured glioblastoma U87 cells were divided into four groups：overexpression group（HULC-over）and its vector control group（VEC），silent expression group（HULC- siRNA）and its negative control group（NC）.Quantitative real- time polymerase chain reaction PCR（qRT-PCR）was used to verify the expression levels of HULC. CCK8 proliferation assay and colony formation assay were adopted to monitor the proliferation of glioblastoma U87 cells. Flow cytometry was utilized to detect the apoptosis of glioblastoma U87 cells. By injecting U87 cells，we divided the orthotopic xenograft mouse model into HULC- over group（n=10），VEC group（n=10），HULC-siRNA group（n=10）and NC group（n=10）accordingly. The survival of the mice in each group was observed. The expression of Ki67 was analyzed by immunohistochemistry. 【Results】 The expression level of HULC was significantly higher in HULC-over group than that in VEC group and significantly lower in HULC-siR NA group than that in NC group（P < 0.01）. The cell proliferation ability was significantly increased in HULC-over group compared with that in VEC group and significantly decreased in HULC- siRNA group compared with that in NC group（P < 0.01 on days2，3and4）. The colony formation rates in VEC group，HULC-over group，NC group and HULC-siRNA group were，respectively，（34.47 ± 1.56）% ，（95.4 ± 2.74）% ，（23.83 ± 0.92）% and （10.23 ± 0.61）% ，which revealed that overexpression of HULC elevated the colony formation rate and silencing expression of HULC reduced the colony formation rate（P < 0.01）. The early apoptosis rates in VEC group，HULC- over group，NC group and HULC- siRNA group were，respectively，（3.55±0.56）% ，（0.09±0.01）% ，（2.89±0.67）% ，and（7.13±0.14）% ，which showed that overexpression of HULC elevated the early apoptosis rate and silencing expression of HULC reduced the early apoptosis rate （P <0.01）. The survival curve of nude mouse indicated shorter survival time in HULC-over group than that in VEC group and longer survival time in HULC-siRNA group than that in NC group（P < 0.05）. Ki67 protein expression was up-regulated in the HULC-over group compared with that in VEC group and down-regulated in the HULC-siRNA group compared with that in NC group（P < 0.05）.【Conclusion】LncRNA HULC can enhance the growth of glioblastoma U87 cells in vitro and in vivo.

Efficacy and Safety of Aspirin Combined with Clopidogrel in the Treatment of Progressing Stroke ：A Meta-analysis / 中国药房

OBJECTIVE：To sy stematically evaluate the efficacy and safety of a spirin combined with clopidogrel in the treatment of progressing stroke. METHODS ：Retrieved from the Cochrane library ，PubMed，Embase，Clinical trials.gov ，CBM， VIP，Wanfang database and CNKI databases ，randomized controlled trials （RCTs）about aspirin combined with clopidogrel （trial group）versus aspirin or clopidogrel alone （control group ）in the treatment of progressing stroke were collected. After literature screening and data extraction ，the quality of literatures were evaluated with bias risk assessment tool recommended by Cochrane system evaluator manual 5.2. Meta-analysis was performed by using Rev Man 5.3 software. RESULTS ：A total of 27 RCTs involving 2 854 patients were enrolled. The results of Meta-analysis showed that response rate of trial group was significantly higher than aspirin group [RR ＝1.31，95％CI（1.26，1.37），P＜0.000 01]；Neurological deficit score （NDS）of trial group was significantly lower than control group [MD ＝－3.80，95％CI（－5.30，－2.30），P＜0.000 01]；National Institutes of Health Stroke Scale Score in trial group was significantly lower than aspirin group [MD ＝－3.72，95％CI（－5.25，－2.20），P＜0.000 01] and clopidogrel group [MD ＝－2.44，95％CI（－4.14，－0.73），P＝0.005]. Results of subgroup analysis showed that NDS score of trial group was significantly lower than control group after 14 d of treatment [MD ＝－2.19，95％CI（－3.11，－1.27），P＜0.000 01]，15 d of treatment [MD ＝－5.73，95％CI（－10.65，－0.81），P＝0.02] and 28 d of treatment [MD ＝－3.45，95％CI（－4.24，－2.67），P＜ 0.000 01]. Compared with trial group ，there was no statistical significance in response rate with clopidogrel group ，the incidence of ADR with clopidogrel group ，the incidence of bleeding event with clopidogrel group ，and mortality with control group （P＞0.05）. CONCLUSIONS：Aspirin combined with clopidogrel in the ； treatment of progressive stroke ，can improve the efficacy and improve neurological deficit symptoms in the short term ，but can not reduce the incidence of ADR or the mortality during E-mail：wuyanzi89@126.com the treatment.