Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Multiplatform tear proteomic profiling reveals novel non-invasive biomarkers for diabetic retinopathy.

OBJECTIVES: To investigate a comprehensive proteomic profile of the tear fluid in patients with diabetic retinopathy (DR) and further define non-invasive biomarkers. METHODS: A cross-sectional, multicentre study that includes 46 patients with DR, 28 patients with diabetes mellitus (DM), and 30 healthy controls (HC). Tear samples were collected with Schirmer strips. As for the discovery set, data-independent acquisition mass spectrometry was used to characterize the tear proteomic profile. Differentially expressed proteins between groups were identified, with gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further developed. Classifying performance of biomarkers for distinguishing DR from DM was compared by the combination of three machine-learning algorithms. The selected biomarker panel was tested in the validation cohort using parallel reaction monitoring mass spectrometry. RESULTS: Among 3364 proteins quantified, 235 and 88 differentially expressed proteins were identified for DR when compared to HC and DM, respectively, which were fundamentally related to retina homeostasis, inflammation and immunity, oxidative stress, angiogenesis and coagulation, metabolism, and cellular adhesion processes. The biomarker panel consisting of NAD-dependent protein deacetylase sirtuin-2 (SIR2), amine oxidase [flavin-containing] B (AOFB), and U8 snoRNA-decapping enzyme (NUD16) exhibited the best diagnostic performance in discriminating DR from DM, with AUCs of 0.933 and 0.881 in the discovery and validation set, respectively. CONCLUSIONS: Tear protein dysregulation is comprehensively revealed to be associated with DR onset. The combination of tear SIR2, AOFB, and NUD16 can be a novel potential approach for non-invasive detection or pre-screening of DR. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2100054263. https://www.chictr.org.cn/showproj.html?proj=143177 . Date of registration: 2021/12/12.

Revealing new insights: Two-center evidence of microplastics in human vitreous humor and their implications for ocular health.

Microplastics (MPs), an emerging environmental contaminant, have raised growing health apprehension due to their detection in various human biospecimens. Despite extensive research into their prevalence in the environment and the human body, the ramifications of their existence within the enclosed confines of the human eye remain largely unexplored. Herein, we assembled a cohort of 49 patients with four ocular diseases (macular hole, macular epiretinal membrane, retinopathy and rhegmatogenous retinal detachment) from two medical centers. After processing the samples with an optimized method, we utilized Laser Direct Infrared (LD-IR) spectroscopy and Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS) to analyze 49 vitreous samples, evaluating the characteristics of MPs within the internal environment of the human eye. Our results showed that LD-IR scanned a total of 8543 particles in the composite sample from 49 individual vitreous humor samples, identifying 1745 as plastic particles, predominantly below 50 µm. Concurrently, Py-GC/MS analysis of the 49 individual samples corroborated these findings, with nylon 66 exhibiting the highest content, followed by polyvinyl chloride, and detection of polystyrene. Notably, correlations were observed between MP levels and key ocular health parameters, particularly intraocular pressure and the presence of aqueous humor opacities. Intriguingly, individuals afflicted with retinopathy demonstrated heightened ocular health risks associated with MPs. In summary, this research provides significant insights into infiltration of MP pollutants within the human eye, shedding light on their potential implications for ocular health and advocating for further exploration of this emerging health risk.

Abdominal core training in table tennis players / Treinamento do centro abdominal em jogadores de tênis de mesa / Entrenamiento del núcleo abdominal en jugadores de tenis de mesa

ABSTRACT Introduction The current teaching mode of table tennis in China is satisfactory, but there are still some problems that are the focus of physical education teachers, such as the low efficiency of sports training. Objective Study the effect of abdominal core training on table tennis teaching. Methods Volunteers trained in table tennis at a physical education college were divided into the experimental and control group. Before and after the beginning of the experiment, table tennis students' physical indices and overall physical scores were obtained under a parameterized protocol. Results The overall score of the experimental group resulted from 7.355 (± 1.827) to 9.072 (± 1.992) before training, and the mean difference was 1.2581 points (P < 0.05), indicating a significant difference. The control group score increased from 7.606 (± 1.937) to 7.989 (± 1.440) before training, and the mean difference was 0.1976, P > 0.05, indicating no significant difference. Conclusion Compared with the current way of teaching table tennis, the scheme proposed in this paper showed better sports efficiency and could help students to improve their physical quality and sports ability. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O atual modo de ensino do tênis de mesa na China é satisfatório, mas ainda existem alguns problemas que são o foco dos professores de educação física, como a baixa eficiência do treinamento esportivo. Objetivo Estudar o efeito do treinamento do centro abdominal no ensino do tênis de mesa. Métodos Voluntários formados em tênis de mesa em uma faculdade de educação física foram divididos em grupo experimental e de controle. Antes e depois do início da experiência, foram obtidos os índices físicos dos alunos de tênis de mesa e a pontuação física geral sob um protocolo parametrizado. Resultados A pontuação geral do grupo experimental resultou em 7,355 (± 1,827) para 9,072 (± 1,992) antes do treinamento, e a diferença média foi de 1,2581 pontos (P < 0,05), indicando uma diferença significativa. A pontuação do grupo de controle aumentou de 7,606 (± 1,937) para 7,989 (± 1,440) antes do treinamento, sendo a diferença média de 0,1976, P > 0,05, indicando que não houve diferença significativa. Conclusão Em comparação com o atual modo de ensino do tênis de mesa, o esquema proposto neste trabalho apresentou melhor eficiência esportiva podendo ajudar os estudantes a melhorar a sua qualidade física e habilidade esportiva. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El modo de enseñanza actual del tenis de mesa en China es satisfactorio, pero todavía hay algunos problemas que son el centro de atención de los profesores de educación física, como la baja eficiencia del entrenamiento deportivo. Objetivo Estudiar el efecto del entrenamiento del núcleo abdominal en la enseñanza del tenis de mesa. Métodos Los voluntarios entrenados en tenis de mesa en una escuela de educación física se dividieron en grupo experimental y grupo de control. Antes y después del inicio del experimento, se obtuvieron los índices físicos de los alumnos de tenis de mesa y la puntuación física global bajo un protocolo parametrizado. Resultados La puntuación global del grupo experimental pasó de 7,355 (± 1,827) a 9,072 (± 1,992) antes del entrenamiento, y la diferencia media fue de 1,2581 puntos (P < 0,05), lo que indica una diferencia significativa. La puntuación del grupo de control aumentó de 7,606 (± 1,937) a 7,989 (± 1,440) antes del entrenamiento, y la diferencia media fue de 0,1976, P > 0,05, lo que indica que no hubo diferencias significativas. Conclusión En comparación con la forma actual de enseñar el tenis de mesa, el esquema propuesto en este trabajo presentaba una mayor eficacia deportiva y podía ayudar a los alumnos a mejorar su calidad física y su capacidad deportiva. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

TRANSIENT PARADOXICAL WORSENING OF VISION DUE TO GRAVITATIONAL SHIFT OF SUBRETINAL FLUID AFTER PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To report an atypical treatment-related complication from photodynamic therapy in central serous chorioretinopathy patient and explain its mechanism. METHODS: History, physical examination, and imaging data were retrospectively reviewed and obtained from the electronic medical records of the patient. RESULTS: A central serous chorioretinopathy patient with several focal leakage spots near the superotemporal arcade was treated with half-fluence verteporfin photodynamic therapy. The patient complained of worse vision after the treatment. Examination showed relocation of subretinal fluid from the superior macula to the central and submacular area, explained by a gravitational shift of subretinal fluid and the predisposing factor of a previously weakened junction between the retinal pigment epithelium and neurosensory retina. Without further treatment, the fluid reabsorbed, and the patient's vision returned to normal. CONCLUSION: This is the first report to describe this transient atypical adverse visual outcome early after photodynamic therapy in a central serous chorioretinopathy patient, caused by a gravitational shift of viscous subretinal fluid.

Comparative Analysis of Multiplex Platforms for Detecting Vitreous Biomarkers in Diabetic Retinopathy.

Purpose: To evaluate the feasibility of using the Proximity Extension Assay (PEA) platform to detect biomarkers in vitreous and to compare the findings with results obtained with an electrochemiluminescent (ECL) sandwich immunoassay. Methods: Vitreous samples from patients with proliferative diabetic retinopathy (PDR) and non-diabetic controls were tested using two different proteomics platforms. Forty-one assays were completed with the ECL platform and 459 with the PEA platform. Spearman's rank correlation coefficient (rs ) was used to determine the direction and strength of the relationship between protein levels detected by both platforms. Results: Three hundred sixty-six PEA assays detected the tested protein in at least 25% of samples, and the difference in protein abundance between PDR and controls was statistically significant for 262 assays. Seventeen ECL assays yielded a detection rate ≥ 25%, and the difference in protein concentration between PDR and controls was statistically significant for 13 proteins. There was a subset of proteins that were detected by both platforms, and for those the Spearman's correlation coefficient was higher than 0.8. Conclusions: PEA is suitable for the analysis of vitreous samples, showing a strong correlation with the ECL platform. The detection rate of PEA panels was higher than the panels tested with ECL. The levels of several proinflammatory and angiogenic cytokines were significantly higher in PDR vitreous compared to controls. Translational Relevance: This study provides new information on the yields of small-volume assays that can detect proteins of interest in ocular specimens, and it identifies patterns of cytokine dysregulation in PDR.

LncRNA Linc-PINT inhibits miR-523-3p to hamper retinoblastoma progression by upregulating Dickkopf-1 (DKK1).

Emerging evidences indicated that long non-coding RNAs (LncRNAs) regulated the pathogenesis of retinoblastoma (RB). However, up until now, the role of LncRNA Linc-PINT in the regulation of RB progression is still largely unknown. The present study identified LncRNA Linc-PINT as a tumor suppressor to hinder RB development by regulating miR-523-3p/Dickkopf-1 (DKK1) axis. Mechanistically, Linc-PINT was low-expressed, while miR-523-3p was high-expressed in RB cells, compared to the normal retinal epithelial cells (ARPE-19). Further gain- and loss-function experiments verified that both upregulation of Linc-PINT and miR-523-3p downregulation slowed down cell growth, invasion and migration, and promoted cell apoptosis in RB cells, but Linc-PINT ablation and miR-523-3p overexpression promoted malignant phenotypes in RB cells. In addition, the dual-luciferase reporter gene system and RNA pull-down assay validated that Linc-PINT positively regulated DKK1 expressions by sponging miR-523-3p, and Linc-PINT inhibited RB progression by regulating miR-523-3p/DKK1 axis. Functionally, we found that both miR-523-3p overexpression and DKK1 silence abrogated the anti-cancer effects of overexpressed Linc-PINT on RB cells. Finally, Linc-PINT inhibited tumorigenicity of RB cells in xenograft mice models. In general, analysis of the data suggested that Linc-PINT inhibited miR-523-3p to upregulate DKK1, resulting in the inhibition of RB, and we demonstrated that Linc-PINT and miR-523-3p could be utilized as potential diagnostic and therapeutic biomarkers for RB in clinic.

Clinical and Optical Coherence Tomography Angiographic Features in Patients with Postcataract Stenotrophomonas maltophilia Endophthalmitis.

PURPOSE: To report the clinical presentations and optical coherence tomography (OCT) angiographic features of patients with postcataract surgery endophthalmitis due to Stenotrophomonas maltophilia. Methods. A retrospective observational study of 4 patients who developed S. maltophilia endophthalmitis after cataract surgery. Pars plana vitrectomy (PPV) was performed to control the infection. Patients were followed up for six months. Complete ophthalmological examination results were collected before and after PPV. RESULTS: Patients' response to PPV therapy was excellent and the infection was cured in all cases. OCTA showed that, at the one-month follow-up, the vascular density (VD) and perfusion density (PD) in the superficial capillary plexus (SCP) were significantly lower than those in healthy collateral eyes. As time went on, the SCP-VD and SCP-PD values gradually improved. CONCLUSIONS: With early PPV, the infection caused by S. maltophilia can be cured. OCTA provides a quantitative noninvasive assessment to evaluate the severity and prognosis of patients with S. maltophilia endophthalmitis.

Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy.

Purpose: To investigate the relationship between proangiogenic and inflammatory cytokines in concurrent vitreous, aqueous, and plasma samples from patients with proliferative diabetic retinopathy (PDR). Methods: Vitreous, aqueous, and plasma samples were analyzed using multiplex immunoassay for 10 PDR-related cytokines (IL-6, IL-8, TNF-α, monocyte chemoattractant protein-1 [MCP-1], macrophage inflammatory protein-1ß [MIP-1ß], VEGF receptor 1 [Flt-1], placental growth factor [PlGF], VEGF-A, VEGF-C, VEGF-D). A total of 17 patients with PDR and 7 controls were included. The primary outcome was correlation of cytokines in vitreous, aqueous, and plasma. The secondary outcome was the comparison of cytokine levels in controls and diabetics with and without recent anti-VEGF injection. Results: The following factors were elevated in diabetics compared with controls: vitreous IL-6, IL-8, TNF-α, MCP-1, MIP-1ß, PlGF, and VEGF-A; and aqueous IL-6, IL-8, PlGF, and VEGF-C (all P < 0.05). Vitreous and aqueous IL-8, PlGF, and VEGF-A were significantly correlated in patients with PDR (all P < 0.05). Plasma cytokines were not correlated with those in vitreous and aqueous (all P > 0.05). Vitreous and aqueous IL-6, IL-8, TNF-α, PlGF, and VEGF-A differed among controls and diabetics with and without recent anti-VEGF injection (all P < 0.05). In one-to-one comparisons, aqueous VEGF-A levels were lower in diabetic patients who had recent anti-VEGF injection compared with those who did not (P = 0.01). Conclusions: In this proof-of-concept study, IL-8, VEGF-A, and PlGF demonstrated a strong correlation in vitreous and aqueous of patients with PDR. The aqueous may serve as a proxy for vitreous for some cytokines involved in PDR. Recent anti-VEGF injections decreased VEGF-A levels in aqueous, but did not significantly affect other cytokines, suggesting a role for other targeted therapies in PDR management.

Improved Outcomes in Patients with Retinal Detachment after Implementation of a Silicone Oil Registry and Phone Call Reminder System.

PURPOSE: This retrospective study was performed to assess the clinical impact in reducing silicone oil (SO)-related complications such as keratopathy of a registry and appointment reminder system for patients with complicated retinal detachment (RD) who underwent pars plana vitrectomy (PPV) with SO tamponade. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 87 eyes of 87 patients who received SO tamponade were included. METHODS: The study was carried out at Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG). Patients were divided into those who received SO before (control group, n = 48) or after (treatment group, n = 39) implementation of an SO registry and patient reminder system in 2014. Patient records were reviewed to identify clinical characteristics and outcomes. MAIN OUTCOME MEASURES: The primary outcome measure was the difference in the rate of loss to follow-up before versus after the implementation of the registry and reminder system. Secondary outcomes were the duration of SO tamponade, keratopathy rate, and intraocular pressure (IOP) at the last visit before SO removal. RESULTS: Forty-eight patients were included in the control group, and 39 patients were included in the treatment group. The number of patients lost to follow-up was 23 (47.9%) in the control group versus 6 (15.4%) in the treatment group (P = 0.0015). The mean duration before SO removal was 79.6±91.7 weeks in the control group and 36.3±31.5 weeks in the treatment group (mean±standard deviation [SD]) (P = 0.015). Keratopathy developed in 33.3% of patients in the control group and 12.8% of patients in the treatment group (P = 0.0425). Mean IOP at the last visit before SO removal was 13.0±5.2 mmHg (mean±SD) in the control group and 13.3±7 mmHg (mean±SD) in the treatment group (P > 0.05). CONCLUSIONS: A phone call appointment reminder system for patients with complicated RD who underwent PPV and SO tamponade reduced the rate of loss to follow-up and the duration of SO tamponade, correlating with a reduction in the rate of keratopathy.

Repair mechanism of mesenchymal stem cells derived from nasal mucosa in orbital fracture.

OBJECTIVE: Mesenchymal stem cells (MSCs) derived from nasal mucosa are featured by high division and differentiation capacity, with large nuclei, obvious nucleoli and weak cytoplasmic basophily. Imaging examination, typically CT scan, is the gold standard for the diagnosis of orbital fracture. METHODS: We isolated MSCs derived from goat nasal mucosa and built the calcification model so as to investigate the repair mechanism of nasal mucosa-derived MSCs in orbital fracture. Expressions of osteogenic markers Runx2, OCN, OPN and BSP were detected using western blot. RESULTS: Nasal mucosa-derived MSCs were successfully isolated and passaged. Nestin was detected by immunofluorescence assay in the cells of the third generation. It was further confirmed that the isolated cells were nasal mucosa-derived MSCs. As indicated by alizarin red staining, the calcification model in nasal mucosa-derived MSCs was successfully built. The relative expressions of Runx2 and OCN reached the highest level after osteogenic induction for 7 d, and the expressions of OPN and BSP were also high. But at 10 d, the expressions of all markers declined somewhat. At 14 d, the expressions of OPN and BSP reached the peak, but without significant differences compared with those at 7 d. CONCLUSION: The present study suggested that the repair effect of nasal mucosa-derived MSCs in orbital fracture is achieved by facilitating the expressions of osteogenic markers Runx2, OCN, OPN and BSP. However, the pathways of actions are unknown and further studies are required to elucidate the concrete mechanism.

RNAi targeting Nogo Receptor enhanced survival and proliferation of murine retinal ganglion cells during N-methyl-D-aspartate-induced optic nerve crush.

We investigated the effects of lentivirus-mediated RNAi targeting of Nogo Receptor (NgR) on the proliferation and survival of murine retinal ganglion cells (mRGCs) in vitro and in vivo. Cultured mRGCs and C57BL/6 male mice were divided into 4 experimental groups: blank, model [100 µM N-methyl-D-aspartate (NMDA)], nscRNA (100 µM NMDA+ nscRNA vectors) and siNgR (100 µM NMDA+ siNgR vectors). CCK-8 and flow cytometry analyses revealed that silencing NgR enhanced proliferation, cell cycling and survival of NMDA-treated mRGCs. H&E staining showed that NgR silencing enhanced mRGC cell density and reduced angiogenesis in NMDA-treated retinal tissues. TUNEL assays showed that mRGC apoptosis was significantly diminished by NgR silencing in NMDA-treated retinal tissues. Western blotting and qRT-PCR analysis in NMDA-treated mRGCs and murine retinal tissues revealed that NgR silencing resulted in downregulation of RhoA signaling (RhoA and ROCK2). Western blotting showed that levels of activated Bax and cleaved caspase 3 were decreased, while Bcl-2 and pro-caspase 3 were increased in NMDA-treated mRGCs and murine retinal tissues, which corroborated the decreased apoptosis. These findings indicate that NgR gene silencing increases proliferation and survival of mRGCs in NMDA-treated murine retinas, which suggests a potential for therapeutic application to preventing optic nerve damage.

Effects of microRNA-211 on proliferation and apoptosis of lens epithelial cells by targeting SIRT1 gene in diabetic cataract mice.

Our study aimed at exploring the effects of miR-211 on the proliferation and apoptosis of lens epithelial cells in diabetic cataract mice by targetting NAD+-dependent histone deacetylase sirtulin 1 (SIRT1). Healthy male mice were assigned into normal and diabetic cataract groups. Blood glucose, lens turbidity, and apoptosis were measured. Lens epithelial cells were classified into the normal, blank, negative control (NC), miR-211 mimics, miR-211 inhibitors, siRNA-SIRT1, and miR-211 inhibitors + siRNA-SIRT1 groups. MiR-211, Bcl-2, Bax, p53, and SIRT1 expressions of each group were detected. Cell proliferation, cycle and apoptosis were tested by MTT assay and flow cytometry. MiR-211 can specifically bind to SIRT1 according to the luciferase system. SIRT1 protein concentration was strongly positive in normal mice and weakly positive in diabetic cataract mice. Apoptosis index of diabetic cataract mice was higher than the normal mice. Compared with normal mice, the expressions of miR-211, Bax, and p53 increased in diabetic cataract mice, while the Bcl-2 and SIRT1 expressions decreased. In comparison with the blank and NC groups, the expressions of miR-211, Bax, and p53 increased, while Bcl-2 and SIRT1 expressions decreased, and the proliferation decreased and apoptosis rate increased in the miR-211 mimics and siRNA-SIRT1 groups; the results were contradicting for the miR-211 inhibitor group. MiR-211 could promote apoptosis and inhibit proliferation of lens epithelial cells in diabetic cataract mice by targetting SIRT1.

Combined Surgery for Simultaneous Treatment of Congenital Ptosis and Coexisting Strabismus.

PURPOSE: To evaluate the clinical outcomes of single-stage surgery for treatment of patients with congenital ptosis and coexisting strabismus. METHODS: A retrospective analysis was performed on 10 patients (17 eyes) with congenital ptosis and coexisting strabismus. Patients were treated with levator resection or frontalis suspension for ptosis and ocular muscle surgery for strabismus, performed as a single-stage procedure. Levator resection was performed in 9 patients (15 eyes) and frontalis muscle flap suspension was performed in 1 patient (2 eyes) with blepharophimosis. Seven patients (11 eyes) simultaneously underwent exotropia correction, and inferior oblique myectomy was performed in 3 patients (3 eyes) with congenital superior oblique palsy. RESULTS: Satisfactory efficacy of single-stage surgery for correction of congenital ptosis and coexisting strabismus was achieved without complications. CONCLUSIONS: Comprehensive preoperative examination is vital to determine the appropriate diagnosis and guide surgical decision-making. Single-stage surgery for congenital ptosis and coexisting strabismus is effective and a shortened treatment period is beneficial to patients. [J Pediatr Ophthalmol Strabismus. 2017;54(5):288-294.].

Ultrasound Microbubbles Enhance the Neuroprotective Effect of Mouse Nerve Growth Factor on Intraocular Hypertension-Induced Neuroretina Damage in Rabbits.

Ultrasound microbubble combined optic protection drugs have obvious protective effect on optic nerve damage. This way of targeting drug delivery is becoming more simple, not through the whole body metabolism, avoiding drug via blood circulation when facing the decomposition and the environment in the interference and destruction process of drugs, to maximize the guarantee to reach target organs of drug concentration and to reache the maximum therapeutic effect. The technique of ultrasound microbubbles is safe, controllable, nonimmunogenic, and repeatable. It provides us with a novel idea in the administration of neuroprotective drugs.