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Stereotactic removal of intracerebral hematoma is a routine procedure for treating hypertensive intracerebral hemorrhage, but the complex sequence of operations limits its adoption. We explored the application of a novel surgical technique for the removal of spontaneous intracerebral hematomas. The surgical technique based on computed tomography (CT) images was used in hematoma projection and surgical planning. Markers placed on the scalp based on an Android smartphone app allowed the installation of a stereotactic head frame to facilitate the selection of the best trajectory to the hematoma center for removing the hematoma. Forty-two patients with spontaneous intracerebral hemorrhage were included in the study, including 33 cases of supratentorial hemorrhage, 5 cases of cerebellum hemorrhage, and 4 cases of brain stem hemorrhage. The surgical technique combined with the stereotactic head frame helped the tip of the drainage tube achieve the desired position. The median surgical time was 45 (range 25-75) min. The actual head frame operating time was 10 (range 5-15) min. Target alignment performed by the surgical technique was accurate to ≤ 10.0 mm in all 42 cases. No patient experienced postoperative rebleeding. In 33 cases of supratentorial intracerebral hemorrhage, an average evacuation rate of 77.5% was achieved at postoperative 3.1 ± 1.4 days, and 29 (87.9%) cases had a residual hematoma of < 15 ml. The novel surgical technique helped to quickly and effortlessly localize hematomas and achieve satisfactory hematoma removal. Clinical application of the stereotactic head frame was feasible for intracerebral hemorrhage in various locations.
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Hemorragia Cerebral/cirugía , Drenaje/métodos , Hematoma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Técnicas Estereotáxicas , Adulto , Anciano , Hemorragia Cerebral/diagnóstico por imagen , Drenaje/tendencias , Estudios de Factibilidad , Femenino , Hematoma/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/tendencias , Tempo Operativo , Técnicas Estereotáxicas/tendencias , Tomografía Computarizada por Rayos X/métodosRESUMEN
The Ate1 arginyltransferase (R-transferase) is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. Ate1 arginylates N-terminal Asp, Glu, or (oxidized) Cys. The resulting N-terminal Arg is recognized by ubiquitin ligases of the N-end rule pathway. In the yeastSaccharomyces cerevisiae, the separase-mediated cleavage of the Scc1/Rad21/Mcd1 cohesin subunit generates a C-terminal fragment that bears N-terminal Arg and is destroyed by the N-end rule pathway without a requirement for arginylation. In contrast, the separase-mediated cleavage of Rec8, the mammalian meiotic cohesin subunit, yields a fragment bearing N-terminal Glu, a substrate of the Ate1 R-transferase. Here we constructed and used a germ cell-confinedAte1(-/-)mouse strain to analyze the separase-generated C-terminal fragment of Rec8. We show that this fragment is a short-lived N-end rule substrate, that its degradation requires N-terminal arginylation, and that maleAte1(-/-)mice are nearly infertile, due to massive apoptotic death ofAte1(-/-)spermatocytes during the metaphase of meiosis I. These effects ofAte1ablation are inferred to be caused, at least in part, by the failure to destroy the C-terminal fragment of Rec8 in the absence of N-terminal arginylation.
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Apoptosis , Metafase , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Proteolisis , Separasa/metabolismo , Espermatocitos/metabolismo , Aminoaciltransferasas/genética , Aminoaciltransferasas/metabolismo , Animales , Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Masculino , Ratones , Ratones Noqueados , Proteínas Nucleares/genética , Fosfoproteínas/genética , Separasa/genéticaRESUMEN
A previous report has confirmed the existence and clinical significance of vasculogenic mimicry (VM) in glioma. However, its conclusions about the negative clinical significance of VM in glioblastoma are based on a small group of patients and, thus, might be unconvincing. The aim of the present study was to reevaluate the clinical significance of VM in glioblastoma. Patients were classified as VM-positive or VM-negative according to CD34 and periodic acid-Schiff staining. The association between VM and the clinical characteristics of the patients was analyzed. Univariate and multivariate analyses were carried out to identify the independent prognostic factors for overall survival using the Cox regression hazard model. Survival times were estimated using the Kaplan-Meier method and compared using the log-rank test. Of all 86 glioblastomas, 23 were found to have VM. The presence of VM in glioblastoma was not associated with gender, age, Karnofsky performance status, hydrocephalus, tumor burden, microvessel density, tumor relapse, or the extent of tumor resection. The univariate and multivariate analyses revealed that VM is an independent prognostic factor for overall survival. The median survival time for patients with VM was 11.17 months compared with 16.10 months for those without VM (P = 0.017). In addition to VM, an age of 65 years or older, a KPS of 60 or less, a large tumor burden are significant prognostic factors for patient survival. Our data suggest that VM might be an independent adverse prognostic factor in newly diagnosed GBM, further prospective studies are needed to answer this question.
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Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/patología , Glioblastoma/irrigación sanguínea , Glioblastoma/patología , Adolescente , Adulto , Anciano , Antígenos CD34/análisis , Antígenos CD34/biosíntesis , Neoplasias Encefálicas/mortalidad , Femenino , Glioblastoma/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
Studies on ischemia/reperfusion (I/R) injury suggest that exogenous neural stem cells (NSCs) are ideal candidates for stem cell therapy reperfusion injury. However, NSCs are difficult to obtain owing to ethical limitations. In addition, the survival, differentiation, and proliferation rates of transplanted exogenous NSCs are low, which limit their clinical application. Our previous study showed that neuregulin1ß (NRG1ß) alleviated cerebral I/R injury in rats. In this study, we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1ß on PC12 cells injured by oxygen-glucose deprivation/reoxygenation (OGD/R). Our results found that 5 and 10 nM NRG1ß promoted the generation and proliferation of NSCs. Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1ß improved the level of reactive oxygen species, malondialdehyde, glutathione, superoxide dismutase, nicotinamide adenine dinucleotide phosphate, and nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial damage in injured PC12 cells; these indexes are related to ferroptosis. Research has reported that p53 and solute carrier family 7 member 11 (SLC7A11) play vital roles in ferroptosis caused by cerebral I/R injury. Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4 (GPX4) was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells, but this change was alleviated after co-culturing NSCs with damaged PC12 cells. These findings suggest that NSCs pretreated with NRG1ß exhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.
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OBJECTIVE: To explore the effects of trunk training using motor imagery on trunk control and balance function in patients with stroke. METHODS: One hundred eligible stroke patients were randomly divided into a control group and trial group. The control group was given routine rehabilitation therapy, while the trial group was given routine rehabilitation therapy and trunk training using motor imagery. RESULTS: Prior to treatment, there was no significant difference between the two groups (P > 0.05) in Sheikh's trunk control ability, Berg rating scale (BBS), Fugl-Meyer assessment (FMA), movement length, movement area, average front-rear movement speed, average left-right movement speed, and surface electromyography (sEMG) signal of the bilateral erector spinae and rectus abdominis. After treatment, Sheikh's trunk control ability, FMA, and BBS in the two groups were significantly higher than those before treatment (P < 0.05). The movement length, movement area, the average front-rear movement speed, and the average left-right movement speed in the two groups decreased significantly (P < 0.05). The differences of these indicators between the two groups were statistically significant (P < 0.05). After treatment, the rectus abdominis and erector spinae on the affected side of the two groups improved when compared with those before treatment (P < 0.05). The rectus abdominis and erector spinae on the healthy side of the trial group descended after treatment (P < 0.05), while little changes were observed on the healthy side of the control group after treatment (P > 0.05). The rectus abdominis and erector spinae on the affected side of the trial group improved when compared with those in the control group (P < 0.05). There was no significant difference between the two groups in the decline of abdominalis rectus and erector spinal muscle on the healthy side. CONCLUSION: Trunk training using motor imagery can significantly improve the trunk control ability and balance function of stroke patients and is conducive to promoting the recovery of motor function.
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Objective: To underscore the paramount significance of incorporating comprehensive rehabilitation therapy as a crucial aspect of managing lymphedema caused by breast cancer surgery, and to illuminate our first-hand experience and insights gained in utilizing this approach. Methods: We present a case report of a breast cancer survivor who had been suffering from persistent left upper-limb edema for over 15 years, who was effectively treated with a combination of conventional rehabilitation (seven-step decongestion therapy) and a comprehensive rehabilitation program (seven-step decongestion therapy, along with core and respiratory function training, as well as functional brace wearing). The efficacy of the rehabilitation therapy was evaluated through a comprehensive assessment. Results: Although the patient underwent the conventional rehabilitation program for one month, only limited improvement was observed. However, after an additional month of comprehensive rehabilitation treatment, the patient exhibited significant improvement in both lymphedema and the overall function of the left upper limb. The patient's progress was quantified by measuring the reduction in arm circumference, which demonstrated a notable decrease. Furthermore, improvements in joint range of motion were observed, with forward flexion of the shoulder enhancing by 10°, forward flexion improving by 15°, and elbow flexion increasing by 10°. In addition, manual muscular strength tests revealed an increase in strength from Grade 4 to Grade 5. The patient's quality of life was also significantly improved, as evidenced by the increase in the Activities of Daily Living score from 95 to 100 points, the increase in the the Functional Assessment of Cancer Therapy: Breast score from 53 to 79 points, and the decrease in the Kessler Psychological Distress Scale score from 24 to 17 points. Conclusion: While seven-step decongestion therapy has been shown to be effective in reducing upper-limb lymphedema caused by breast cancer surgery, it has limitations in treating more chronic cases of the condition. However, when combined with core and respiratory function training and functional brace wearing, seven-step decongestion therapy has been shown to be even more effective in reducing lymphedema and improving limb function, ultimately leading to significant improvements in quality of life.
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Understanding the spatio-temporal variations of gross primary productivity (GPP) of terrestrial ecosystem and its relationship with climatic factors can provide important basis for vegetation restoration and protection. Based on meteorological data and three public GPP datasets (EC-LUE GPP, GLASS GPP, and NIRv GPP), we syste-matically analyzed the spatial-temporal variations of GPP and its response to climate change in China during 1982-2017. All the results based on the three GPP datasets showed that the annual and seasonal GPP in China increased annually from 1982 to 2017, with that in 1998 and 2002 significantly being higher than the average level during the study period, and that in 1989 and 1992 significantly being lower than the average annual GPP. From 1982 to 2017, GPP showed a significant upward trend in most regions of China, with the regions with significant increases accounting for 75.7%, 73.0%, and 69.6% of the whole study area, respectively. There was a significant positive correlation between annual GPP and precipitation and temperature, but spatial heterogeneity was strong. Among them, the regions with positive correlation between GPP and temperature were mainly distributed in Northwest and Central China, while the regions with positive correlation between GPP and precipitation were mainly distributed in North China. There was obvious spatial-temporal heterogeneity in regions that GPP being affected by temperature and precipitation in different seasons. Temperature was the limiting factor of GPP in spring, autumn and winter, while summer GPP was mainly affected by precipitation.
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Cambio Climático , Ecosistema , China , Estaciones del Año , TemperaturaRESUMEN
Ischemic stroke is a common cerebrovascular disease and recovering blood flow as early as possible is essential to reduce ischemic damage and maintain neuronal viability, but the reperfusion process usually causes additional damage to the brain tissue in the ischemic area, namely ischemia reperfusion injury. The accumulated studies have revealed that transplantation of exogenous neural stem cells (NSCs) is an ideal choice for the treatment of ischemia reperfusion injury. At present, the source and efficacy of exogenous NSCs after transplantation is still one of the key issues that need to be resolved. In this study, human umbilical cord mesenchymal stem cells (hUC-MSCs) were obtained and induced into NSCs byadding growth factor and neuregulin1ß (NRG1ß) was introduced during the differentiation process of NSCs. Then, the rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established, and the therapeutic effects were evaluated among groups treated by NRG1ß, NSCs and NSCs pretreated with 10 nM NRG1ß (NSCs-10 nM NRG1ß) achieved through intra-arterial injection. Our data show that the NSCs-10 nM NRG1ß group significantly improves neurobehavioral function and infarct volume after MCAO/R, as well as cerebral cortical neuron injury, ferroptosis-related indexes and mitochondrial injury. Additionally, NSCs-10 nM NRG1ß intervention may function through regulating the p53/GPX4/SLC7A11 pathway, and reducing the level of ferroptosis in cells, further enhance the neuroprotective effect on injured cells.
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Células Madre Mesenquimatosas , Células-Madre Neurales , Daño por Reperfusión , Animales , Humanos , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/terapia , Células Madre Mesenquimatosas/metabolismo , Células-Madre Neurales/metabolismo , Ratas , Daño por Reperfusión/terapia , Cordón UmbilicalRESUMEN
OBJECTIVE: To investigate the effects of paired associated stimulation (PAS) with different stimulation position on motor cortex excitability and upper limb motor function in patients with cerebral infarction. METHOD: A total of 120 volunteers with cerebral infarction were randomly divided into four groups. Based on conventional rehabilitation treatment, the PAS stimulation group was given the corresponding position of PAS treatment once a day for 28 consecutive days. The MEP amplitude and RMT of both hemispheres were assessed before and after treatment, and a simple upper limb Function Examination Scale (STEF) score, simplified upper limb Fugl-Meyer score (FMA), and improved Barthel Index (MBI) were used to assess upper limb motor function in the four groups. RESULTS: Following PAS, the MEP amplitude decreased, and the RMT of abductor pollicis brevis (APB) increased on the contralesional side, while the MEP amplitude increased and the RMT of APB decreased on the ipsilesional side. After 28 consecutive days the scores of STEF, FMA, and MBI in the bilateral stimulation group were significantly better than those in the ipsilesional stimulation group and the contralesional stimulation group, but there was no significant difference in the scores of STEF, FMA, and MBI between the ipsilesional stimulation group and the contralesional stimulation group. CONCLUSION: The excitability of the motor cortex can be changed when the contralesional side or the ipsilesional side was given the corresponding PAS stimulation, while the bilateral PAS stimulation can more easily cause a change of excitability of the motor cortex, resulting in better recovery of the upper limb function.
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Infarto Cerebral/fisiopatología , Infarto Cerebral/rehabilitación , Terapia por Estimulación Eléctrica , Corteza Motora/fisiopatología , Extremidad Superior/fisiopatología , Adulto , Potenciales Evocados Motores , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Rehabilitación de Accidente Cerebrovascular/métodos , Estimulación Magnética TranscranealRESUMEN
OBJECTIVE: For studying the functions of periostin (POSTN) further, the recombinant plasmid and lentiviral vector for human periostin were constructed. The mRNA and protein expressions of POSTN were tested after the infection with the shRNA plasmid and lentivirus of POSTN in primary keloid fibroblasts (KFb). METHODS: We designed a specific sequence of small hair RNA targeting POSTN gene which containing both sense and antisense oligo DNA of the targeting sequence. It was cloned into the vectors to construct a plasmid and a lentiviral vector. The plasmid was converted into the competent DH5α E.coli, which confirmed by PCR and sequencing. Then the viral vector and the packed systemic vector were co-transfected 293T cells to get the lentivirus. KFb was infected with the plasmid and lentivirus. The expressions of POSTN in KFb were detected by RT-PCR and Western blotting. MTT was used to examine the proliferation of KFb and SFb. RESULTS: The expression of POSTN mRNA in KFb infected with plasmid reduced 43% compared with negative control cells (1.98±0.03 vs 1.12±0.03, F=688.291, P<0.001). The mRNA and protein levels of POSTN in KFb infected with the lentivirus reduced 46% (0.44±0.09 vs 0.81±0.07, F=90.06, P<0.001) and 45% (0.29±0.04 vs 0.53±0.09, F=33.43, P<0.001), respectively, compared with negative control cells. Compared with negative control cells, the decreased proliferation rates were 19%, 14%, 18% in 48 h, 72 h, 96 h, respectively in KFb infected with the lentivirus. CONCLUSION: The expression of POSTN in primary keloid fibroblasts reduced after infecting plasmid or lentiviral shRNA expression vector targeting human POSTN, which will be a basis to the further function study of POSTN.
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Moléculas de Adhesión Celular/genética , Fibroblastos/metabolismo , ARN Interferente Pequeño/genética , Moléculas de Adhesión Celular/biosíntesis , Línea Celular , Vectores Genéticos/genética , Humanos , Queloide/patología , Lentivirus/genética , Lentivirus/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , TransfecciónRESUMEN
OBJECTIVE: To probe into the role of periostin in the formation of scars and investigate its reaction to hydrocortisone. METHODS: Primary fibroblasts were cultured in vitro, then RT-PCR and immunocytochemical technique were used to examine the expressions of mRNA and preotein of periostin respectively in 24 samples of keloid fibroblasts (KFb), hypertrophic scar fibroblasts (HFb) and normal skin fibroblasts (SFb). RESULTS: The mRNA levels of periostin in KFb (1.645+/-0.549) and HFb (1.084+/-0.396) were both higher than that in SFb (0.274+/-0.215, P<0.05). After hydrocortisone was added, the mRNA levels of periostin in KFb and HFb were both decreased by 32% and 47% respectively (P<0.05 ); The protein of periostin distributed mainly in the endochylema around the nucleus of fibroblasts. The protein levels of periostin in KFb (91.815+/-0.961) and HFb (70.166+/-2.250) were both higher than that in SFb (41.011 +/- 1.576, P<0.01). CONCLUSION: The expressions of periostin were increased in the fibroblasts of hyperplasic scars, which could be inhibited by hydrocortisone. periostin may affect the function of fibroblasts of hyperplasic scars. periostin may be a cicatrix specific gene.
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Moléculas de Adhesión Celular/metabolismo , Cicatriz Hipertrófica/metabolismo , Fibroblastos/metabolismo , Hidrocortisona/farmacología , Queloide/metabolismo , Quemaduras/patología , Moléculas de Adhesión Celular/genética , Cicatriz Hipertrófica/etiología , Cicatriz Hipertrófica/patología , Femenino , Fibroblastos/citología , Humanos , Queloide/patología , Masculino , Cicatrización de HeridasRESUMEN
OBJECTIVE: To study the effect of BAM bone grafting combined with inactivated autologous porous bone flap in repairing skull defect in rats. METHODS: Seventy-two Wistar rats with skull defect were randomly divided into control group, inactivated autologous bone flap group (AB group), BAM bone-induced artificial bone material group (BAM group), and inactivated autologous bone flap with BAM bone-induced artificial bone group (BAM+AB group). The bone healing was evaluated with micro-CT and the new bone formation was assessed with histological staining at 1, 2, and 3 months after modeling. RESULTS: Inactivated porous bone flap combined with BAM bone-induced artificial bone effectively induced vascular and fibrous tissue regeneration and osteogenesis in the cranial defects. With the inactivated porous bone flap as the scaffold, BAM bone-induced artificial bone obviously promoted the restoration of the skull appearance in the rats with cranial defects. CONCLUSION: Inactivated autologous bone flap group and BAM bone-induced artificial bone material can promote skull healing and restoration of the original skull appearance, and can be used for reconstruction of the local anatomy of the skull surface.
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Regeneración Ósea/fisiología , Sustitutos de Huesos , Trasplante Óseo/métodos , Osteogénesis/fisiología , Cráneo/lesiones , Cicatrización de Heridas/fisiología , Animales , Distribución Aleatoria , Ratas , Ratas Wistar , Cráneo/cirugíaRESUMEN
Objective: Ovariectomized mice were used to simulate the symptoms of postmenopausal women with osteoporosis, and observe the effects of PEMF treatment on expression of Osx, Ocn, TRAP, and CTSK in ovariectomized mice. Methods: Thirty-week-old wild-type C57BL/6 mice were randomly divided into three groups (n=10, each group): sham operation group, ovariectomy (OVX) group, and PEMF group. Mice in the sham group underwent sham ovariectomy, while mice in the remaining two groups were ovariectomized. On postoperative day two, mice in the PEMF treatment group received PEMF treatment at a frequency of 8 Hz and an intensity of 3.8 mT for one hour daily for four weeks. At the same time, mice in the remaining two groups were placed in the PEMF treatment area under power-down state daily, similar to that in the PEMF group. After four weeks, all relevant indicators were tested. Results: (1) Compared with mice in the sham group, the number of trabecular bones significantly decreased, the thickness of the trabecular bone became thinner, the number of osteoclasts significantly increased, the gene expression of Osx and Ocn significantly decreased, and the gene expression of TRAP and CTSK significantly increased in the OVX group (P<0.01). (2) Compared with the blank controls without operation, the number of osteoblasts increased in the PEMF group. (3) Compared with the OVX group, the number of osteoclasts significantly decreased, the expression of Osx and Ocn significantly increased, and the gene expression of TRAP and CTSK significantly decreased in the PEMF group (P<0.01). Conclusion: PEMF treatment can significantly promote bone formation, which may be realized through inhibition of osteoclast formation, achieving bone morphological protection. PEMFs can significantly upregulate Osx and Ocn osteogenesis-related genes, which affect bone formation, and downregulate TRAP and CTSK osteoclast-related genes, which affect bone resorption. PEMFs may be used to treat postmenopausal osteoporosis by regulating Osx, Ocn, TRAP, and CTSK gene expression.
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BACKGROUND: Phacoemulsification yields successful outcomes in eyes with standard cataract. Though techniques have been improved, it is still challenging to perform phacoemulsification in cases of hard cataracts for difficulty in nuclear management and much more complications. This study aimed at describing and evaluating the efficacy and safety of a peripheral radial chop technique to remove hard cataracts. METHODS: In this prospective study conducted between January 2003 and January 2004, 107 consecutive eyes with hard cataract underwent modified phacoemulsification surgery with peripheral radial chop technique by the Bausch & Lomb Millennium phacoemulsifier with preset parameters of power less than 30%; vaccum, 150 mmHg; and bottle height, 85 cm when a DP8145 phaco tip was used, and vaccum, 380 mmHg; bottle height, 95 cm when a DP8245 phaco tip was used. RESULTS: The mean ultrasonic power was 14.7% (range 9% to 19%), ultrasonic time was 1.98 minutes (range 1.55 to 3.18 minutes). At 1, 7 and 30 days postoperatively, the eyes with uncorrected visual acuity 0.5 or better accounted for 76.42%, 87.16% and 90.67% respectively. At 1 month, the endothelial cell loss rate was 9.74% (range 8% to 17%). There were 6 cases of posterior capsule rupture in an early period of study. No serious intraoperative or postoperative complications were noted. CONCLUSIONS: The peripheral radial chop technique was effective without serious complications in hands of an experienced surgeon.
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Facoemulsificación/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Facoemulsificación/efectos adversos , Estudios ProspectivosRESUMEN
Vasculogenic mimicry (VM), a process involving the formation of a tubular structure by highly invasive and genetically dysregulated tumor cells, can supplement the function of blood vessels to transport nutrients and oxygen to maintain the growth of tumor cells in many malignant tumors. We aimed to explore the existence of VM and its clinical significance in medulloblastoma in this study. VM was identified in 9 out of 41 (22%) medulloblastoma tissues. Immunohistochemical studies revealed that the presence of VM was associated with the expression of MMP-2, MMP-14, EphA2 and laminin 5γ2. Tumor tissues with VM were associated with lower microvessel density (MVD), which was indirect evidence of the blood supply function of VM. Survival analysis and log-rank tests showed that patients with VM had shorter overall survival time than those without VM. Multivariate analysis and the Cox proportional hazards model identified VM as independent prognostic factor for overall survival. Our results confirmed the existence of VM for the first time and revealed that VM is a strong independent prognostic factor for survival in patients with medulloblastoma.
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Neoplasias Cerebelosas/irrigación sanguínea , Meduloblastoma/irrigación sanguínea , Adolescente , Adulto , Neoplasias Cerebelosas/metabolismo , Neoplasias Cerebelosas/patología , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Masculino , Meduloblastoma/metabolismo , Meduloblastoma/patología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Adulto JovenRESUMEN
Immunotoxins have shown great promise as an alternative treatment for brain malignancies such as gliomas, but their failure to penetrate into the tumor mass remains a major problem. Mesenchymal stem cells exhibit tropism to tumor tissue and may serve as a cellular vehicle for the delivery and local production of antitumor agents. In this study, we used human bone marrow-derived mesenchymal stem cells (hMSCs) as a vehicle for the targeted delivery of EphrinA1-PE38, a very specific immunotoxin against the EphA2 receptor that is overexpressed in gliomas. hMSCs were transduced with adenovirus to express secretable EphrinA1-PE38. Our invitro assays confirmed the expression, release and selective killing effect of the immunotoxin produced by hMSCs. Furthermore, the intratumoral injection of engineered hMSCs was effective at inhibiting tumor growth in a malignant glioma tumor model. These results indicate that gene therapy utilizing EphrinA1-PE38-secreting hMSCs may provide a novel approach for the local treatment of malignant gliomas.