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BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0 vs. 35.0%, P =0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9 vs. 32.8%, P =0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P =0.173; OS: log-rank P =0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P >0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was noninferior to OCTG in both short-term and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.
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Estudios de Factibilidad , Gastrectomía , Laparoscopía , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Gastrectomía/métodos , Gastrectomía/efectos adversos , Masculino , Laparoscopía/efectos adversos , Laparoscopía/métodos , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Muñón Gástrico/cirugía , Muñón Gástrico/patología , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analyzed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% vs. 59.0%; P <0.001), pathological complete response rate (14.36% vs. 6.41%; P =0.002) and major pathological response rate (39.49% vs. 26.15%; P =0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P =0.694) and the proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P =0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P =0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence [odds ratio 0.62 (95% CI 0.41-0.92); P =0.018]. No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P =0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.
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Gastrectomía , Laparoscopía , Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Masculino , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Gastrectomía/efectos adversos , Anciano , Laparoscopía/efectos adversos , Resultado del Tratamiento , China , Estudios Retrospectivos , Inmunoterapia/métodos , Inmunoterapia/efectos adversos , Puntaje de Propensión , AdultoRESUMEN
INTRODUCTION: Lipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance. METHODS: Untargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes. RESULTS: Long-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage. CONCLUSION: LCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS.
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Neutrophil aggregation and clearance are important factors affecting neuroinflammatory injury during acute ischemic stroke. Emerging evidence suggests that energy metabolism is essential for microglial functions, especially microglial phagocytosis, which determines the degree of brain injury. Here, we demonstrate that Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenic acid (DHA), promotes the phagocytosis of neutrophils by microglia, thereby reducing neutrophil accumulation in the brain and alleviating neuroinflammation in the ischemic brain. Further studies reveal that RvD1 reprograms energy metabolism from glycolysis to oxidative phosphorylation (OXPHOS), providing sufficient energy for microglial phagocytosis. Moreover, RvD1 enhances microglial glutamine uptake and stimulates glutaminolysis to support OXPHOS to boost ATP production depending on adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Overall, our results reveal that RvD1 reprograms energy metabolism to promote the microglial phagocytosis of neutrophils after ischemic stroke. These findings may guide perspectives for stroke therapy from modulating microglial immunometabolism.
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Accidente Cerebrovascular Isquémico , Neutrófilos , Humanos , Microglía/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Metabolismo EnergéticoRESUMEN
PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p < 0.05; gadopentetate, p < 0.001) and 28 p. i of gadopentetate. (p < 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p > 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p < 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p < 0.05). CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.
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Cerebro , Compuestos Organometálicos , Animales , Ratones , Atrofia , Encéfalo , Medios de Contraste , Gadolinio , Gadolinio DTPA , Hiperalgesia , Isquemia , Ratones Endogámicos C57BL , Neuronas , DolorRESUMEN
Pericytes are present tight around the intervals of capillaries, play an essential role in stabilizing the blood-brain barrier, regulating blood flow and immunomodulation, and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in ischemic stroke. We previously show that iptakalim, an ATP-sensitive potassium (K-ATP) channel opener, exerts protective effects in neurons, and glia against ischemia-induced injury. In this study we investigated the impacts of iptakalim on pericytes contraction in stroke. Mice were subjected to cerebral artery occlusion (MCAO), then administered iptakalim (10 mg/kg, ip). We showed that iptakalim administration significantly promoted recovery of cerebral blood flow after cerebral ischemia and reperfusion. Furthermore, we found that iptakalim significantly inhibited pericytes contraction, decreased the number of obstructed capillaries, and improved cerebral microcirculation. Using a collagen gel contraction assay, we demonstrated that cultured pericytes subjected to oxygen-glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation, whereas iptakalim treatment (10 µM) notably restrained pericyte contraction from 6 h during reoxygenation. We further showed that iptakalim treatment promoted K-ATP channel opening via suppressing SUR2/EPAC1 complex formation. Consequently, it reduced calcium influx and ET-1 release. Taken together, our results demonstrate that iptakalim, targeted K-ATP channels, can improve microvascular disturbance by inhibiting pericyte contraction after ischemic stroke. Our work reveals that iptakalim might be developed as a promising pericyte regulator for treatment of stroke.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adenosina Trifosfato , Animales , Ratones , Microcirculación , Pericitos , Propilaminas , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Oridonin, a natural diterpenoid compound extracted from a Chinese herb, has been proved to exert anti-oxidative stress effects in various disease models. The aim of the present study was to investigate the protective effects of oridonin on oxidative stress-induced endothelial injury in ischaemic stroke. We found oridonin repaired blood-brain barrier (BBB) integrity presented with upregulation of tight junction proteins (TJ proteins) expression, inhibited the infiltration of periphery inflammatory cells and neuroinflammation and thereby reduced infarct volume in ischaemic stroke mice. Furthermore, our results showed that oridonin could protect against oxidative stress-induced endothelial injury via promoting nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2). The specific mechanism could be the activation of AKT(Ser473)/GSK3ß(Ser9)/Fyn signalling pathway. Our findings revealed the therapeutic effect and mechanism of oridonin in ischaemic stroke, which provided fundamental evidence for developing the extracted compound of Chinese herbal medicine into an innovative drug for ischaemic stroke treatment.
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Diterpenos de Tipo Kaurano/farmacología , Endotelio/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Biomarcadores , Barrera Hematoencefálica/metabolismo , Permeabilidad Capilar , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Endotelio/efectos de los fármacos , Endotelio/patología , Glucosa/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Inmunohistoquímica , Accidente Cerebrovascular Isquémico/etiología , Masculino , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oxígeno/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Extracellular vesicles (EVs), as a novel intercellular communication carrier transferring cargo microRNAs (miRNAs), could play important roles in the brain remodeling process after ischemic stroke. However, the detailed mechanisms involved in EVs derived miRNAs-mediated cellular interactions in the brain remain unclear. Several studies indicated that microRNA-98 (miR-98) might participate in the pathogenesis of ischemic stroke. Here, we showed that expression of miR-98 in penumbra field kept up on the first day but dropped sharply on the 3rd day after ischemic stroke in rats, indicating that miR-98 could function as an endogenous protective factor post-ischemia. Overexpression of miR-98 targeted inhibiting platelet activating factor receptor-mediated microglial phagocytosis to attenuate neuronal death. Furthermore, we showed that neurons transferred miR-98 to microglia via EVs secretion after ischemic stroke, to prevent the stress-but-viable neurons from microglial phagocytosis. Therefore, we reveal that EVs derived miR-98 act as an intercellular signal mediating neurons and microglia communication during the brain remodeling after ischemic stroke. The present work provides a novel insight into the roles of EVs in the stroke pathogenesis and a new EVs-miRNAs-based therapeutic strategy for stroke.
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Isquemia Encefálica/genética , Vesículas Extracelulares/metabolismo , MicroARNs/metabolismo , Microglía/metabolismo , Neuronas/metabolismo , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Humanos , Accidente Cerebrovascular Isquémico , Fagocitosis , RatasRESUMEN
Background: Glioblastoma (GBM) is one of the most malignant and aggressive primary brain tumors. The incurability of glioblastoma is heavily influenced by the glioma microenvironment. FTY720, a potent immunosuppressant, has been reported to exert anti-tumor effects in glioblastoma. However, the impact of FTY720 on the glioma microenvironment remains unclear. Methods: We examined the effects of FTY720 on the distribution and polarization of glioma-associated microglia and macrophages (GAMs) in glioma-bearing rats using immunofluorescence staining. qRT-PCR and Western blotting were used to detect the expressions of CXCR4 and MAPK pathway-related signal molecules on microglia in the coculture system. The levels of inflammatory factors were tested via ELISA. Wound healing assay and Matrigel invasion assay were used to determine the migration and invasion of C6 glioma cells. Results: We discovered that FTY720 could inhibit the growth, migration, and invasion of glioma by targeting GAMs to impede their effect on glioma cells. Simultaneously, FTY720 could block the chemoattraction of GAMs by inhibiting MAPK-mediated secretion of IL-6 through increased internalization of CXCR4. Moreover, microglia and macrophages are polarized from pro-glioma to an anti-tumor phenotype. Conclusion: These results provide novel insights into the inhibitory effects of FTY720 on glioma by targeting GAMs-glioma interaction in the tumor microenvironment.
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Antineoplásicos/administración & dosificación , Clorhidrato de Fingolimod/administración & dosificación , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Microglía/efectos de los fármacos , Receptores CXCR4/metabolismo , Microambiente Tumoral/efectos de los fármacos , Aloinjertos , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Polaridad Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Glioblastoma/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Microglía/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Receptores CXCR4/genética , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To compare the superior-level facet joint violations (FJV) between robot-assisted (RA) percutaneous pedicle screw placement and conventional open fluoroscopic-guided (FG) pedicle screw placement in a prospective cohort study. METHODS: This was a prospective cohort study without randomization. One-hundred patients scheduled to undergo RA (n = 50) or FG (n = 50) transforaminal lumbar interbody fusion were included from February 2016 to May 2018. The grade of FJV, the distance between pedicle screws and the corresponding proximal facet joint, and intra-pedicle accuracy of the top screw were evaluated based on postoperative CT scan. Patient demographics, perioperative outcomes, and radiation exposure were recorded and compared. Perioperative outcomes include surgical time, intraoperative blood loss, postoperative length of stay, conversion, and revision surgeries. RESULTS: Of the 100 screws in the RA group, 4 violated the proximal facet joint, while 26 of 100 in the FG group had FJV (P = 0.000). In the RA group, 3 and 1 screws were classified as grade 1 and 2, respectively. Of the 26 FJV screws in the FG group, 17 screws were scored as grade 1, 6 screws were grade 2, and 3 screws were grade 3. Significantly more severe FJV were noted in the FG group than in the RA group (P = 0.000). There was a statistically significant difference between RA and FG for overall violation grade (0.05 vs 0.38, P = 0.000). The average distance of pedicle screws from facet joints in the RA group (4.16 ± 2.60 mm) was larger than that in the FG group (1.92 ± 1.55 mm; P = 0.000). For intra-pedicle accuracy, the rate of perfect screw position was greater in the RA group than in the FG group (85% vs 71%; P = 0.017). No statistically significant difference was found between the clinically acceptable screws between groups (P = 0.279). The radiation dose was higher in the FG group (30.3 ± 11.3 vs 65.3 ± 28.3 µSv; P = 0.000). The operative time in the RA group was significantly longer (184.7 ± 54.3 vs 117.8 ± 36.9 min; P = 0.000). CONCLUSIONS: Compared to the open FG technique, minimally invasive RA spine surgery was associated with fewer proximal facet joint violations, larger facet to screw distance, and higher intra-pedicle accuracy.
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Vértebras Lumbares/cirugía , Tornillos Pediculares , Procedimientos Quirúrgicos Robotizados/métodos , Fusión Vertebral/métodos , Articulación Cigapofisaria/cirugía , Adulto , Anciano , Femenino , Fluoroscopía , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: To compare one-time accuracy rate between simulated freehand (SFH) and navigation simulated (NS) pedicle screw insertion, assuming no second chance to correct screws. METHODS: A simulated, comparative, cross-sectional study was conducted on 69 patients undergoing lumbar spine surgery. An intraoperative registration system captured the planned point of entry and trajectory of pedicle screws for both SFH under direct visualization and NS under navigation-aided visualization. Pedicle screw insertion was simulated for each captured image (370 screws) using Surgimap. Rajasekaran's method helped evaluate the point of entry accuracy and trajectory. RESULTS: Accuracy rate was better for the NS method (97.8%) than for the SFH method (63.8%). Of 370 screws in the SFH group, 134 penetrated the cortex, with 31 resulting in >4 mm penetration. Of 370 screws in the NS group, 8 penetrated the cortex, <4 mm penetration. Of 134 misplaced screws in the SFH group, 64 were due to error in the point of entry, 63 were due to error in the trajectory angle, and 7 were due to both errors. Of 8 errors in the NS group, 7 were due to the point of entry. CONCLUSIONS: Intraoperative navigation had significantly better one-time accuracy of pedicle screw insertion than freehand insertion and should be used to avoid injury to the pedicle and surrounding tissue from screw reinsertion.
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Vértebras Lumbares/cirugía , Neuronavegación/métodos , Procedimientos Neuroquirúrgicos/métodos , Tornillos Pediculares , Anciano , Simulación por Computador , Estudios Transversales , Femenino , Humanos , Imagenología Tridimensional , Desplazamiento del Disco Intervertebral/cirugía , Masculino , Persona de Mediana Edad , Reoperación , Estenosis Espinal/cirugía , Espondilolistesis/cirugíaRESUMEN
Several previous studies have demonstrated that cyclindependent kinase (CDK)5 expression serves an important role in promoting the development of malignant tumours. We have previously reported that CDK5 suppresses gastric tumourigenesis. The aim of the present study was to investigate the mechanistic basis of CDK5. The results of immunoprecipitation and western blot analysis demonstrated that CDK5 could interact with serine/threonineprotein phosphatase 2A (PP2A). The use of an inhibitor of PP2A in CDK5overexpressing gastric cancer (GC) cell lines antagonized CDK5mediated suppression in GC cells. Further analysis revealed that PP2A expression was downregulated in GC and patients with low levels of PP2A had worse survival outcomes than those with high levels of PP2A (P=0.035). Therefore, the present study provided a novel mechanism for CDK5mediated tumour suppression, suggesting that CDK5 may be an attractive target for future therapeutic strategies for treating GC. In addition, low levels of PP2A may indicate a tendency for poor prognosis in patients with GC.
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Quinasa 5 Dependiente de la Ciclina/metabolismo , Proteína Fosfatasa 2/metabolismo , Neoplasias Gástricas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Ácido Ocadaico/farmacología , Pronóstico , Unión Proteica , Proteína Fosfatasa 2/antagonistas & inhibidores , Estómago/patología , Neoplasias Gástricas/mortalidadRESUMEN
AIM: To evaluate the predictive value of the expression of chromosomal maintenance (CRM)1 and cyclin-dependent kinase (CDK)5 in gastric cancer (GC) patients after gastrectomy. METHODS: A total of 240 GC patients who received standard gastrectomy were enrolled in the study. The expression level of CRM1 and CDK5 was detected by immunohistochemistry. The correlations between CRM1 and CDK5 expression and clinicopathological factors were explored. Univariate and multivariate survival analyses were used to identify prognostic factors for GC. Receiver operating characteristic analysis was used to compare the accuracy of the prediction of clinical outcome by the parameters. RESULTS: The expression of CRM1 was significantly related to size of primary tumor (P = 0.005), Borrmann type (P = 0.006), degree of differentiation (P = 0.004), depth of invasion (P = 0.008), lymph node metastasis (P = 0.013), TNM stage (P = 0.002) and distant metastasis (P = 0.015). The expression of CDK5 was significantly related to sex (P = 0.048) and Lauren's classification (P = 0.011). Multivariate Cox regression analysis identified that CRM1 and CDK5 co-expression status was an independent prognostic factor for overall survival (OS) of patients with GC. Integration of CRM1 and CDK5 expression could provide additional prognostic value for OS compared with CRM1 or CDK5 expression alone (P = 0.001). CONCLUSION: CRM1 and CDK5 co-expression was an independent prognostic factors for GC. Combined CRM1 and CDK5 expression could provide a prognostic model for OS of GC.
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Adenocarcinoma/mortalidad , Quinasa 5 Dependiente de la Ciclina/análisis , Carioferinas/análisis , Receptores Citoplasmáticos y Nucleares/análisis , Neoplasias Gástricas/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Quinasa 5 Dependiente de la Ciclina/metabolismo , Femenino , Gastrectomía , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Carioferinas/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Receptores Citoplasmáticos y Nucleares/metabolismo , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Proteína Exportina 1RESUMEN
Several previous studies have demonstrated that CDK5 or p27 expression in gastric cancer are associated with overall survival. We have previously reported that tumor suppressive function of CDK5 is related to p27. The aim of this study was to investigate correlation between the clinicopathological parameters and overall survival with different CDK5/p27 expression statuses in 244 gastric cancer patients using immunohistochemistry. Low CDK5 expression was detected in 93 cases (38.11%) and low p27 in 157 cases (64.34%). The expression of CDK5 was significantly related to sex (P = 0.034) and Lauren's classification (P = 0.013). The expression of p27 was significantly related to sex (P = 0.012), differentiation (P = 0.003), TNM stage (P = 0.013) and lymph node metastasis (P = 0.001). Based on the combined expression of CDK5 and p27, we classified the patients into four subtypes: CDK5 Low/p27 Low (n = 69), CDK5 High/p27 Low (n = 88), CDK5 Low/p27 High (n = 24) and CDK5 High/p27 High (n = 63). The CDK5 Low/p27 Low expression was closely related to female (P = 0.026), diffuse type (P = 0.027) and lymph node metastasis (P = 0.010). The CDK5 Low/p27 Low patients displayed poorer survival in comparison with the rest of the patients in Kaplan-Meier analysis. No significant overall survival difference was observed among the patients with CDK5 High and/or p27 High expression. In the multivariate analysis, CDK5 and p27 co-expression status was identified as an independent prognostic factor for patients with gastric cancer.
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Neoplasias de Tejido Muscular , Neoplasias Craneales , Hueso Temporal/patología , Anciano , Humanos , MasculinoRESUMEN
OBJECTIVE: To explore the effects of integrin ß3 pathway on the proliferation, migration and extracellular matrix deposition of pulmonary arterial smooth muscle cells (PASMCs) induced by connective tissue growth factor (CTGF). METHODS: PASMCs of SD Rats were cultured in M199 culture system in vitro and the 3rd-7th passages of PASMCs were used in the experiments. The cells were randomly divided into three groups: (1) CONTROL GROUP: culture system contained no any stimulation factor; (2) CTGF group: culture system was added into 50 ng/ml CTGF; (3) CTGF+ anti-integrin ß3 antibody group:culture system was added with 50 ng/ml CTGF and 10 mg/L anti-integrin ß3 antibody. The PASMCs were cultured with 50 ng/ml CTGF and anti-integrin ß3 antibody (0, 5, 10, 15, 20 mg/L) for 24, 48, 72 and 96 h, the proliferation of PASMCs was detected by WST-1 Cell Proliferation Assay Kit. The migration of PASMCs was observed by Transwell cell test under the phase contrast microscope. RT-PCR assay was applied to detect the mRNA expression of collagenI-α1, collagen III-α1 and fibronectin-1 gene of PASMCs. The expression of fibronectin protein was examined by Western blotting and immunohistochemistry. RESULTS: The results of WST-1 test showed that the anti-integrin ß3 antibody inhibited significantly the proliferation of PASMCs induced by CTGF (P < 0.05), among which the inhibition rate of anti-integrin ß3 antibody (10 mg/L) was the most significant. Transwell test results showed that CTGF group of PASMCs migration numbers (25 ± 1.57) were higher than that of the control group (11 ± 2.08, P < 0.01); PASMCs migration numbers of CTGF+ integrin ß3 antibody group (17 ± 4.16) were less than that of the CTGF group (P < 0.05). Compared with the control group, the mRNA expression of collagen typeI-α1 (4.28 ± 0.33), collagen typeIII-α1 (4.41 ± 0.35), fibronectin-1 (4.05 ± 0.33) of PASMCs was increased in CTGF group, with a time-dependence (P < 0.01); Compared with the CTGF group, the mRNA expression of collagen typeI-α1 (3.38 ± 0.30), collagen typeIII-α1 (3.40 ± 0.30), fibronectin-1 (3.12 ± 0.29) of PASMCs was reduced in CTGF+ anti-integrin ß3 antibody group (P < 0.05), which was higher than that of the control group (P < 0.05); Western blot and immunohistochemical tests showed that compared with the control group, CTGF group could stimulate the expression of fibronectin protein of PASMCs (P < 0.01); the anti-integrin ß3 antibody could inhibit the expression of fibronectin protein induced by CTGF(P < 0.01), which was more remarkable than that in the control group (P < 0.01). CONCLUSION: Integrin ß3 pathway can mediate CTGF-induced proliferation, migration and extracellular matrix deposition of PASMCs, CTGF-integrin ß3 signaling pathway may play an important role in pulmonary vascular remodeling.
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Factor de Crecimiento del Tejido Conjuntivo/farmacología , Matriz Extracelular/metabolismo , Integrina beta3/metabolismo , Células Musculares/metabolismo , Arteria Pulmonar/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Masculino , Células Musculares/citología , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Arteria Pulmonar/citología , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Electrochemical behaviors, electrochemical kinetics and electrochemical determination of sulfamethoxazole (SMZ) at both glassy carbon electrode (GCE) and multi-wall carbon nanotubes-Nafion modified glassy carbon electrode (MWCNTs-Nafion/GCE) were investigated by cyclic voltammetry (CV), chronocoulometry (CC), chronoamperometry (CA), linear scan voltammetry (LSV) and amperometric i-t curve. The experimental results showed that the electrochemical oxidation of SMZ was sluggish on GCE, but the oxidation peak current of SMZ increased significantly at MWCNTs-Nafion/GCE in comparison with that at the bare GCE, which indicated that MWCNTs-Nafion/GCE could catalyze the electrochemical oxidation of SMZ very well. The plot of oxidation peak currents versus the square roots of the scanning rates for the redox in the potential range of 10-1,000 mV x s(-1) showed a straight line, as expected for a diffusion-limited electrochemical process for SMZ electrochemical oxidation. At the bare GCE and MWCNTs-Nafion/GCE the oxidation peak current was linearly proportional to the concentration of SMZ over the concentration range 5.0 x 10(-5)-2.5 x 10(-3) mol x L(-1) and 1.0 x 10(-5)-6.0 x 10(-3) mol x L(-1). The detection limits were 1.0 x 10(-5) and 5.0 x 10(-7) mol x L(-1). The relative standard deviation was between 0.85% -1.98% and the recovery was in the range of 98%-101.2%. This MWCNTs-Nafion/GCE could be applied in SMZ electrochemical determination with satisfied results. The proposed method can be applied to the determination of SMZ in tablet samples with satisfied results.
Asunto(s)
Electroquímica/métodos , Nanotubos de Carbono , Sulfametoxazol/química , Catálisis , Electrodos , Polímeros de Fluorocarbono/química , Cinética , Oxidación-Reducción , Sulfametoxazol/análisisRESUMEN
The growth and development of Sanqi in the lack of nutritional elements had been done by the water culture. The results indicated that Sanqi plants had different symptoms in the lack of nutritional elements. According to the symptom the symptomatic list was made in this paper.
Asunto(s)
Panax/crecimiento & desarrollo , Plantas Medicinales/crecimiento & desarrollo , Medios de Cultivo/química , Medios de Cultivo/farmacología , Panax/efectos de los fármacos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Plantas Medicinales/efectos de los fármacosRESUMEN
OBJECTIVE: To compare the effects of the different fertilizing levels on the output, the effective element, the content of heavy-metal, the grade and the ratio of wet to dry of Pinella ternate to obtain the best fertilize ratio on the planting. METHODS: The orthogonal desing method L9 (3(4)) was applied on the comparison between the different fertilization levels. The content of alkaloid was determined by UV spectrophotometer. The content of heavy-metal was determined by atom absorption. RESULTS: The factors that affected the output and the quality of Pinellia ternate were N > P > K. CONCLUSION: The best fertilizer combination is N 25 g/m2 ,P2O5 18 g/m2, K2O9 g/m2 and the application ratio is 2. 8: 2: 1 for them, in which the higher output and the content of alkaloid should be obtained.
Asunto(s)
Alcaloides/análisis , Fertilizantes , Metales Pesados/análisis , Pinellia/química , Plantas Medicinales/química , Nitrógeno , Fósforo , Pinellia/crecimiento & desarrollo , Plantas Medicinales/crecimiento & desarrollo , Potasio , Control de Calidad , Espectrofotometría UltravioletaRESUMEN
OBJECTIVE: To select the main directions and the objects in breeding the high yield of Panax notoginseng by the correlation and path analysis of main agronomic character of P. notoginseng. METHOD: Samples in fifty-two districts of Yunnan and Guangxi were collected. The height of plant, the diameter of stem, the number, length, width, size of leaf and the weight of each root of those samples were measured. RESULT: The greatest contribution to the weight of each root is the size of leaf. CONCLUSION: The size of leaf should be key to the high yield of cultribution of P. notoginseng and the size of leaf especially the width of leaf should be selected in breeding. At the same time, the height of plant and the diameter of stem should be considered.