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Identifying conservation units is crucial for the effective conservation of threatened species. Previous cases are almost exclusively based on large-scale but coarse sampling for genetic structure analyses. Significant genetic structure can occur within a small range, and thus multiple conservation units may exist in narrowly distributed plants. However, small-scale genetic structure is often overlooked in conservation planning especially for wind-pollinated and wind-dispersed trees, largely due to the absence of dense and elaborate sampling. In this study, we focused on a representative endangered relict plant, Metasequoia glyptostroboides. Using both nuclear microsatellites (nSSRs) and chloroplast DNA (cpDNA) fragments, we sampled across the narrow distribution range of this species and determined its conservation units by exploring its genetic structure and historical demography. cpDNA haplotypes were classified into two groups, but mixed in space, suggesting that the existent wild trees of M. glyptostroboides cannot be divided into different evolutionarily significant units. However, using nSSRs, we detected strong spatial genetic structure, with significant genetic differentiation and weak gene flow between the samples in the east of the species' distribution range and other samples. The divergence between the two nSSR groups was dated to the Last Glacial Maximum (c. 19.6 kya), suggesting that such spatial genetic structure has been maintained for a long term. Therefore, these two nSSR groups should be considered as different conservation units, that is, management units, to protect intergroup genetic variations, which is likely to be the outputs of local adaptation. Our findings highlight the necessity to reveal small-scale genetic structure and population demography to improve the conservation strategies of evolutionary potential of endangered plants.
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Objective:To assess the psychometric properties of the Chinese version of 12-item immediate mood scale(IMS-12) in patients with depression.Methods:From January to June 2018, a total of 459 patients with depression recruited from an outpatient clinic by convenient sampling approach.All the subjects were assessed by the Chinese version of the IMS-12, and 43 of them were assessed again at the end of the first week.The 16-item quick inventory of depressive symptomatology (QIDS-SR16), and the generalized anxiety disorder scale-7(GAD-7) were used as validity indicator.The factor structure of the scale was evaluated by exploratory and confirmatory factor analyses.The internal consistency of the Chinese version of the IMS-12 scale was evaluated by Cronbach’s alpha coefficient.The intraclass correlation coefficient (ICC) was used to evaluate test-retest reliability.Pearson’s correlation coefficient was used to evaluate calibration validity.The softwares of SAS 9.4 and Mplus 8.5 were used for statistical analysis.Results:The exploratory factor analysis indicated that the fitting result of the two-factor model was good(including depression and anxiety factors). The results of the confirmatory factor analysis indicated that the factor model fit well and met the reference standard ( χ2/ df=2.82, CFI=0.936, TLI=0.920, RMSEA=0.088). The Cronbach’s alpha coefficient of the Chinese version of the IMS-12 was 0.95, and the ICC for test-retest reliability was 0.85.The correlation coefficients of the total IMS-12 score with the QIDS-SR16 score and with the GAD-7 score were 0.69 and 0.70, respectively. Conclusion:The Chinese version of the IMS-12 has good reliability and validity and is suitable for the clinical assessment of depressive and anxiety symptoms in patients with depression.
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BackgroundThe treatment of patients with depressive disorders is short of targeted outcome assessment. As a secondary outcome that is guided by patient values, quality of life is thus of relatively high evaluative value. In China, there exists a lack of large sample prospective cohort studies evaluating the effect of different treatment protocols on quality of life in patients with acute depressive disorder. ObjectiveTo explore the effects of monotherapy and combination therapy on the quality of life of patients with depressive disorder in acute phase, so as to provide references for optimizing the outcome of treatment for such patients. MethodsA prospective follow-up cohort study from August 24, 2020 to November 29, 2021 was conducted, including 1 330 patients from 22 hospitals across 18 cities in China. All these patients met the diagnostic criteria for depressive episodes, recurrent depressive disorder from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Patients were divided into monotherapy group (n=969) and combination therapy group (n=361) according to the acute phase treatment protocol. At baseline, the end of the first half month as well as the 1st, 2nd, 3rd, 6th, 9th and 12th months of treatment, patients were assessed with Inventory of Depressive Symptomatology Self-report (IDS-SR30), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), Concise Health Risk Tracking Scale (CHRT) and Siehan Disability Scale (SDS). Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) was adopted for assessment at each visit time point of treatment. Spearman correlation analysis was adopted to examine the correlation of quality of life with suicide risk, adverse reactions and impaired social functioning among patients. ResultsAt the end of three months of treatment, the Q-LES-Q-SF score of monotherapy group was higher than that of combination therapy group, and the difference was statistically significant (Z=2.008, P<0.05). The time effects of both treatment protocols possessed statistical significance (F=111.393, P<0.01). At the end of three months of treatment, the Q-LES-Q-SF score was negatively correlated with CHRT and SDS scores, respectively, in both monotherapy group and combination treatment group (r=-0.660, -0.712, -0.634, -0.718, P<0.01). ConclusionBoth monotherapy and combination therapy can facilitate the improvement of the life quality of patients with acute depressive disorder, but monotherapy may achieve better than the combination therapy in this aspect. [Funded by The National Key Research and Development Program of China "Research on the Prevention and Control of Major Chronic Non-communicable Diseases" (number, 2017YFC1311101)]
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OBJECTIVES@#At present, there are many reports about the treatment of cricopharyngeal achalasia by injecting botulinum toxin type A (BTX-A) into cricopharyngeal muscle guided by ultrasound, electromyography or CT in China, but there is no report about injecting BTX-A into cricopharyngeal muscle guided by endoscope. This study aims to evaluate the efficacy of endoscopic BTX-A injection combined with balloon dilatation in the treatment of cricopharyngeal achalasia after brainstem stroke, and to provide a better method for the treatment of dysphagia after brainstem stroke.@*METHODS@#From June to December 2022, 30 patients with cricopharyngeal achalasia due to brainstem stroke were selected from the Department of Rehabilitation Medicine, the First Hospital of Changsha. They were randomly assigned into a control group and a combined group, 15 patients in each group. Patients in both groups were treated with routine rehabilitation therapy, while patients in the control group were treated with balloon dilatation, and patients in the combined group were treated with balloon dilatation and BTX-A injection. Before treatment and after 2 weeks of treatment, the patients were examined by video fluoroscopic swallowing study, Penetration-aspiration Scale (PAS), Dysphagia Outcome Severity Scale (DOSS), and Functional Oral Intake Scale (FOIS) were used to assess the swallowing function.@*RESULTS@#In the combined group, 1 patient withdrew from the treatment because of personal reasons. Two weeks after treatment, the scores of DOSS, PAS, and FOIS in both groups were better than those before treatment (all P<0.01), and the combined group was better than the control group (all P<0.001). The effective rate was 85.7% in the combined group and 66.7% in the control group, with no significant difference between the 2 groups (P>0.05).@*CONCLUSIONS@#BTX-A injection combined with balloon dilatation is more effective than balloon dilatation alone in improving swallowing function and is worthy of clinical application.
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Humanos , Trastornos de Deglución/terapia , Acalasia del Esófago/tratamiento farmacológico , Dilatación/efectos adversos , Toxinas Botulínicas Tipo A/uso terapéutico , Infartos del Tronco Encefálico/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Food fortification is an effective strategy to address vitamin A (VitA) deficiency, which is the leading cause of childhood blindness and drastically increases mortality from severe infections. However, VitA food fortification remains challenging due to significant degradation during storage and cooking. We utilized an FDA-approved, thermostable, and pH-responsive basic methacrylate copolymer (BMC) to encapsulate and stabilize VitA in microparticles (MPs). Encapsulation of VitA in VitA-BMC MPs greatly improved stability during simulated cooking conditions and long-term storage. VitA absorption was nine times greater from cooked MPs than from cooked free VitA in rats. In a randomized controlled cross-over study in healthy premenopausal women, VitA was readily released from MPs after consumption and had a similar absorption profile to free VitA. This VitA encapsulation technology will enable global food fortification strategies toward eliminating VitA deficiency.
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Deficiencia de Vitamina A , Vitamina A , Femenino , Ratas , Animales , Alimentos Fortificados , Estudios Cruzados , Culinaria , MicronutrientesRESUMEN
OBJECTIVES@#Stroke patients may have various sensory-motor disorders, such as spasticity, muscle weakness or sensory damage. Spasticity affects 20% to 40% of stroke patients. Patients with spasticity may have problems such as pain, motor function damage, and the decreased range of motion, which leads to decline of activity and quality of daily life. Extracorporeal shock wave therapy (ESWT) is a technique that can improve post-stroke spasticity. Whole body vibration (WBV), as a passive neuromuscular muscle stimulation technique, can improve the posture control, muscle strength, and muscle work of different people. At present, there are still few studies using WBV combined with ESWT for the treatment of hemiplegic patients with stroke. This study aims to explore the effects of WBV combined with ESWT on spasticity of the affected lower limb and gait function in stroke patients.@*METHODS@#From March 2020 to March 2021, 50 hemiplegic patients with stroke were treated in the Department of Rehabilitation Medicine of the First Hospital of Changsha and they were assigned into a control group and a combined group, 25 cases per group. Both groups carried out conventional treatment, while the control group undertook the ESWT and fake WBV based on conventional treatment, and the combined group undertook ESWT after WBV and conventional treatment. Modified Ashworth Scale (MAS), Lower Extremity portion of the Fugl-Meyer Motor Assessment (FMA-LE), Berg Balance Scale (BBS), and parameters of three-dimensional gait analysis including kinematic parameters (peak value of hip flexion and knee flexion) and spatiotemporal parameters (velocity, cadence and stride length) were assessed before and after 4-week treatment between the 2 groups.@*RESULTS@#After 4 weeks of treatment, MAS scores in 2 groups were lower than before (both P<0.05), and the combined group was lower than the control group (P<0.001); BBS and FMA-LE scores were higher than those before treatment (both P<0.05), and the combined group was higher than the control group (both P<0.001); in the control group, the walking speed, stride frequency, and stride length were higher than those before treatment (all P<0.05), and there was no significant difference between the peak value of flexion hip and peak value of flexion knee (both P<0.05); the peak value of hip flexion, peak value of knee flexion, step speed, step frequency, and stride length in the combined group were higher than those before treatment (all P<0.05), and were higher than those in control group (P<0.05 or P<0.001).@*CONCLUSIONS@#WBV combined with ESWT can improve the spasticity and motor function of the affected lower extremity, balance, and gait in hemiplegic patients with stroke.
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Humanos , Tratamiento con Ondas de Choque Extracorpóreas , Marcha , Hemiplejía/terapia , Espasticidad Muscular/terapia , Accidente Cerebrovascular/complicaciones , Rehabilitación de Accidente Cerebrovascular/métodos , Resultado del Tratamiento , Vibración/uso terapéuticoRESUMEN
COVID-19, caused by SARS-CoV-2, has recently affected over 300,000 people and killed more than 10,000. The manner in which the key immune cell subsets change and their states during the course of COVID-19 remain unclear. Here, we applied single-cell technology to comprehensively characterize transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19. Compared with healthy controls, in patients in the early recovery stage (ERS) of COVID-19, T cells decreased remarkably, whereas monocytes increased. A detailed analysis of the monocytes revealed that there was an increased ratio of classical CD14++ monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1B+ monocytes in the ERS. CD4+ and CD8+ T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naive B cells decreased. Our study identified several novel B cell-receptor (BCR) changes, such as IGHV3-23 and IGHV3-7, and confirmed isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity. Furthermore, integrated analysis predicted that IL-1{beta} and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2 and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting that COVID-19 patients are still vulnerable after hospital discharge. Our identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19. Highlights- The immune response was sustained for more than 7 days in the early recovery stage of COVID-19, suggesting that COVID-19 patients are still vulnerable after hospital discharge. - Single-cell analysis revealed a predominant subset of CD14++ IL1{beta}+ monocytes in patients in the ERS of COVID-19. - Newly identified virus-specific B cell-receptor changes, such as IGHV3-23, IGHV3-7, IGHV3-15, IGHV3-30, and IGKV3-11, could be helpful in the development of vaccines and antibodies against SARS-CoV-2. - IL-1{beta} and M-CSF were discovered as novel mediators of inflammatory cytokine storm, and TNFSF13, IL-2, IL-4, and IL-18 may be beneficial for recovery.
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OBJECTIVE: To compare the incidence and risk factors of superior facet joint violation (FJV) during cortical bone trajectory screw placement in robot-assisted approach versus conventional technique. METHODS: A retrospective study, including 69 patients having cortical bone trajectory (CBT) screw instrumentation for symptomatic degenerated diseases or trauma, was conducted between June 2015 to January 2019. All patients underwent CBT surgery performed by the same team of experienced surgeons. Patients were randomly divided into two groups: a conventional group (CG, 46 cases) and a robot group (RG, 23 cases). The surgical robotic system was used for screw instrumentation in the robot group and the traditional screw instrumentation with fluoroscopic guidance was used in the conventional group. Cortical screws followed a medio-to-lateral path in the transverse plane and a caudal-to-cephalad path in the sagittal plane. Preoperative and postoperative computed tomography (CT) scans were obtained to determine the degree and incidence of FJV. The violation status of facet joint was evaluated according to the modified classification: grade 0, no violation; grade 1, screw shaft, screw head or rod within 1 mm of or abutting the facet joint, but did not enter the articular facet joint; grade 2, screw shaft, screw head or rod clearly in the facet joint. The following factors that may contribute to the occurrence of FJV were analyzed: age, sex, body mass index (BMI), proximal fusion level, fusion length, the side of screw, preoperative vertebral slip, superior facet angle, and degenerative scoliosis. The chi-squared test and Student's t-test were used for analysis of the variables for significance (P < 0.05). RESULTS: FJV occurred in 41.3% of patients in CG and 17.3% of patients in RG. A chi-squared analysis revealed a significantly lower rate of FJV for RG compared with CG (P = 0.04). In the CG, 17 of the 109 cephalad screws were grade 1 (15.6%), and five were grade 2 (4.6%). In the RG, three of the 46 cephalad screws were grade 1 (6.5%), and three were grade 2 (6.5%). There was a statistically significant difference in the incidence of FJV between the left and right screw with fluoroscopy-assisted CBT screw instrumentation (P < 0.05). A significant correlation between scoliosis with the FJV was found in CG (P < 0.05) and in RG (P < 0.05). With regard to superior facet angle, a measurement ≥45° was a significant risk factor of FJV in CG (P < 0.05) and in RG (P < 0.05). CONCLUSIONS: A robot-assisted approach could reduce the incidence of FJV compared with the conventional approach in CBT technique.
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Hueso Cortical/cirugía , Vértebras Lumbares/cirugía , Tornillos Pediculares , Procedimientos Quirúrgicos Robotizados/métodos , Fusión Vertebral/métodos , Articulación Cigapofisaria/lesiones , Anciano , Femenino , Fluoroscopía , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES@#Since the outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly in China and many other countries. The rapid increase in the number of cases has caused widespread panic among people and has become the main public health problem in the world. Severe patients often have difficult breathing and/or hypoxemia after 1 week of onset. A few critically ill patients may not only rapidly develop into acute respiratory distress syndrome, but also may cause coagulopathy, as well as multiple organs failure (such as heart, liver and kidney) or even death. This article is to analyze the predictive role of clinical features in patients with COVID-19 for severe disease, so as to help doctor monitor the severity-related features, restrain the disease progress, and provide a reference for improvement of medical treatment.@*METHODS@#The clinical data of 208 patients with COVID-19 who were isolated and treated in Changsha Public Health Treatment Center from January 17, 2020 to March 14, 2020 were collected. All patients were the mild and ordinary adult patients on admission, including 105 males and 103 females from 19 to 84 (median age 44) years old. According to the "Program for the diagnosis and treatment of novel coronavirus (COVID-19) infected pneumonia (Trial version 7)" issued by the General Office of National Health Committee and Office of State Administration of Traditional Chinese Medicine as the diagnostic and typing criteria. According to progression from mild to severe disease during hospitalization, the patients were divided into a mild group (=183) and a severe transformation group (=25). The clinical features such as age, underlying disease, blood routine, coagulation function, blood biochemistry, oxygenation index, and so on were analyzed. Among them, laboratory tests included white blood cell (WBC), lymphocytes (LYM), neutrophil (NEU), hemoglobin (Hb), platelet (PLT), prothrombin time (PT), plasma fibrinogen (Fib), activated partial prothrombin time (APTT), thrombin time (TT), -dimer, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Cr), creatine kinase (CK), creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), and oxygen partial pressure in arterial blood. Partial pressure of oxygen in arterial blood/fractional concentration of inspiratory oxygen (PaO/FiO) was calculated. The variables with statistical significance were analyzed by logistic regression analysis.@*RESULTS@#Patients in the severe transformation group had more combined underlying diseases than those in the mild group (<0.05). From the perspective of disease distribution, patients in the severe transformation group had more combined hypertension (<0.05). In the severe transformation group, PT was significantly longer, the levels of Fib, ALT, AST, CK, LDH, and CRP were significantly higher than those in the mild group (<0.05 or <0.001), while LYM, ALB, and PaO/FiO were significantly lower than those in the mild group (<0.05 or <0.001). Logistic regression analysis was performed on clinical features with statistically significant differences. Combined with hypertension, LYM, PT, Fib, ALB, ALT, AST, CK, LDH, and CRP as independent variables, and having severe disease or not was the dependent variable. The results show that combined hypertension, decreased LYM, longer PT, and increased CK level were independent risk factors that affected the severity of COVID-19 (<0.05).@*CONCLUSIONS@#The patients with mild COVID-19 who are apt to develop severe diseases may be related to combined hypertension, decreased LYM, and longer PT, and increased CK level. For the mild patients with these clinical features, early intervention may effectively prevent the progression to severe diseases.
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Betacoronavirus , China , Infecciones por Coronavirus , Diagnóstico , Progresión de la Enfermedad , Hospitalización , Pandemias , Neumonía Viral , Diagnóstico , Estudios RetrospectivosRESUMEN
Micronutrient deficiencies affect up to 2 billion people and are the leading cause of cognitive and physical disorders in the developing world. Food fortification is effective in treating micronutrient deficiencies; however, its global implementation has been limited by technical challenges in maintaining micronutrient stability during cooking and storage. We hypothesized that polymer-based encapsulation could address this and facilitate micronutrient absorption. We identified poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate) (1:2:1) (BMC) as a material with proven safety, offering stability in boiling water, rapid dissolution in gastric acid, and the ability to encapsulate distinct micronutrients. We encapsulated 11 micronutrients (iron; iodine; zinc; and vitamins A, B2, niacin, biotin, folic acid, B12, C, and D) and co-encapsulated up to 4 micronutrients. Encapsulation improved micronutrient stability against heat, light, moisture, and oxidation. Rodent studies confirmed rapid micronutrient release in the stomach and intestinal absorption. Bioavailability of iron from microparticles, compared to free iron, was lower in an initial human study. An organotypic human intestinal model revealed that increased iron loading and decreased polymer content would improve absorption. Using process development approaches capable of kilogram-scale synthesis, we increased iron loading more than 30-fold. Scaled batches tested in a follow-up human study exhibited up to 89% relative iron bioavailability compared to free iron. Collectively, these studies describe a broad approach for clinical translation of a heat-stable ingestible micronutrient delivery platform with the potential to improve micronutrient deficiency in the developing world. These approaches could potentially be applied toward clinical translation of other materials, such as natural polymers, for encapsulation and oral delivery of micronutrients.
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Calor , Micronutrientes/administración & dosificación , Microesferas , Administración Oral , Animales , Disponibilidad Biológica , Transporte Biológico , Preparaciones de Acción Retardada , Liberación de Fármacos , Femenino , Humanos , Ácido Hialurónico/química , Absorción Intestinal , Intestinos/fisiología , Hierro/metabolismo , Metacrilatos/química , Ratones , Oxidación-Reducción , Rayos Ultravioleta , Vitamina A/metabolismo , AguaRESUMEN
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
PURPOSE: Paclitaxel is an integral component of primary therapy for breast and epithelial ovarian cancers, but less than half of these cancers respond to the drug. Enhancing the response to primary therapy with paclitaxel could improve outcomes for women with both diseases.Experimental Design: Twelve kinases that regulate metabolism were depleted in multiple ovarian and breast cancer cell lines to determine whether they regulate sensitivity to paclitaxel in Sulforhodamine B assays. The effects of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2) depletion on cell metabolomics, extracellular acidification rate, nicotinamide adenine dinucleotide phosphate, reactive oxygen species (ROS), and apoptosis were studied in multiple ovarian and breast cancer cell lines. Four breast and ovarian human xenografts and a breast cancer patient-derived xenograft (PDX) were used to examine the knockdown effect of PFKFB2 on tumor cell growth in vivo. RESULTS: Knockdown of PFKFB2 inhibited clonogenic growth and enhanced paclitaxel sensitivity in ovarian and breast cancer cell lines with wild-type TP53 (wtTP53). Silencing PFKFB2 significantly inhibited tumor growth and enhanced paclitaxel sensitivity in four xenografts derived from two ovarian and two breast cancer cell lines, and prolonged survival in a triple-negative breast cancer PDX. Transfection of siPFKFB2 increased the glycolysis rate, but decreased the flow of intermediates through the pentose-phosphate pathway in cancer cells with wtTP53, decreasing NADPH. ROS accumulated after PFKFB2 knockdown, which stimulated Jun N-terminal kinase and p53 phosphorylation, and induced apoptosis that depended upon upregulation of p21 and Puma. CONCLUSIONS: PFKFB2 is a novel target whose inhibition can enhance the effect of paclitaxel-based primary chemotherapy upon ovarian and breast cancers retaining wtTP53.
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Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos , Neoplasias Ováricas/metabolismo , Paclitaxel/farmacología , Fosfofructoquinasa-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Expresión Génica , Silenciador del Gen , Humanos , Inmunohistoquímica , Redes y Vías Metabólicas , Ratones , Mutación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Estrés Oxidativo , Fosfofructoquinasa-2/genética , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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
As one of the most important smart materials, fluorescent hydrogel actuators can produce both color and shape changes under external stimuli. In the present work, an effective approach to develop a novel fluorescent hydrogel actuator with pH and thermo dual responsiveness is proposed. Through incorporating pH-responsive perylene tetracarboxylic acid (PTCA), which is a typical fluorescent moiety with aggregation-caused quenching (ACQ) effect, into an anisotropic poly(N-isopropylacrylamide)-polyacrylamide (PNIPAm-PAAm) structure, the obtained hydrogel exhibits stable thermoresponsive shape deformation and switchable fluorescence performance upon a pH trigger. Therefore, fluorescence-quenching-based and actuation-based information can be revealed when exposed to UV light and immersed into warm water, respectively. Moreover, the thermoresponsive actuating behavior can be applied to further hide the fluorescence-quenching-based images. The present work may provide new insights into the design and preparation of novel stimuli-responsive hydrogel actuators.
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Colorantes Fluorescentes/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Temperatura , Fluorescencia , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Objective To investigate the effects of single i.v. subanesthetic dose of ketamine on heart rate, blood pressure and oxygen saturation for antidepressant treatment. Methods Patients with severe depressive disorder were randomized to ketamine group (n=13) and control group (n=14). Ketamine group received ketamine (0.5mg/kg) single injection whereas control group received saline single injection. Escitalopram (10 mg/d) were orally administered for 4 weeks simultaneously. Comparisons were made on the heart rate, blood pressure and oxygen saturation at baseline, 40 min, 100 min, and 280 min after injection between the two groups. Results The main effects of time but not group were significant for all parameters including heart rate, systolic blood pressure and diastolic blood pressure, (P<0.05). Interaction of time×group was significant (P<0.05). All parameters including heart rate (F=16.85, P<0.01), systolic blood pressure (F=15.82, P<0.01) and diastolic blood pressure (F=8.63, P<0.01) with time were significant in ketamine group. The heart rate, systolic blood pressure and diastolic blood pressure in ketamine group were significantly higher at 40 min than at other time points (P<0.05), while were no significant difference among other time points (P>0.05). There was no statistical significance of main effect of time, group and interaction of time×group in oxygen saturation between the two groups (P>0.05). Conclusion Single subanesthetic dose ketamine intravenous drip for antidepressant therapy may cause a transient increase in heart rate and blood pressure.
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Minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) is a challenging technique with a long learning curve. We combined computer-assisted navigation and MI TLIF (CAMISS TLIF) to treat lumbar degenerative disease. This study aimed to evaluate the learning curve associated with computer-assisted navigation MI spine surgery (CAMISS) and TLIF for the surgical treatment of lumbar degenerative disease. Seventy four consecutive patients with lumbar degenerative disease underwent CAMISS TLIF between March 2011 and May 2015; all surgeries were performed by a single surgeon. According to the plateau of the asymptote, the initial 25 patients constituted the early group and the remaining patients comprised the latter group. The clinical evaluation data included operative times, anesthesia times, intraoperative blood losses, days until ambulation, postoperative hospital stays, visual analog scale (VAS) leg and back pain scores, Oswestry disability index (ODI) values, Macnab outcome scale scores, complications, radiological outcomes, and rates of conversion to open surgery. The complexity of the cases increased over the series, but the complication rate decreased (12.00%-6.12%). There were significant differences between the early and late groups with respect to the average surgical times and durations of anesthesia, but no differences in intraoperative blood losses, days until ambulation, postoperative hospital stays, complication rate, VAS, ODI, Macnab outcome scale scores, or solid fusion rates. There was no need for conversion to open procedures in either group. Our study showed that a plateau asymptote for CAMISS TLIF was reached after 25 operations. The later patients experienced shorter operative times and anesthesia durations.
Asunto(s)
Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Fusión Vertebral/métodos , Cirujanos/educación , Cirugía Asistida por Computador/métodos , Adulto , Competencia Clínica/estadística & datos numéricos , Estudios de Cohortes , Evaluación de la Discapacidad , Femenino , Humanos , Curva de Aprendizaje , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/educación , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Enfermedades de la Columna Vertebral/cirugía , Fusión Vertebral/efectos adversos , Fusión Vertebral/educación , Cirugía Asistida por Computador/efectos adversos , Cirugía Asistida por Computador/educación , Resultado del Tratamiento , Escala Visual AnalógicaRESUMEN
Realization of shape memory process in polymeric hydrogels at ambient condition is a significant development to shape memory materials. The sound understanding of the dynamic shape memory process is fundamentally important but limited. Here, a novel shape memory hydrogel with simultaneously switchable fluorescence behavior is developed. The hydrogel is prepared by incorporating a pH-responsive fluorescent molecule, perylene tetracarboxylic acid, into chitosan-based hydrogel, and the assembly and disassembly of chitosan chains into microcrystals upon the trigger of pH are applied as reversible crosslinks to achieve shape memory effect. Therefore, the formation and disassociation of microcrystalline chitosan, and the switchable fluorescence performance happen concurrently, which bring convenience to monitoring the shape memory process by fluorescent imaging. Moreover, the erasable fluorescence behavior also gives the hydrogel potential applications in information storage.
Asunto(s)
Quitosano/química , Fluorescencia , Hidrogeles/química , Perileno/análogos & derivados , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Estructura Molecular , Perileno/química , Polímeros/síntesis química , Polímeros/químicaRESUMEN
Although shape memory polymers have been highlighted widely and developed rapidly, it is still a challenging task to realize complex temporary shapes automatically in practical applications. Herein, a novel shape memory hydrogel with the ability of self-deformation is presented. Through constructing an anisotropic poly(acrylic acid)-polyacrylamide (PAAc-PAAm) structure, the obtained hydrogel exhibits stable self-deformation behavior in response to pH stimulus, and the shapes that formed automatically can be fixed by the coordination between carboxylic groups and Fe3+ ; therefore, self-deformation and shape memory behaviors are integrated in one system. Moreover, the magnitude of auto-deformation and shape memory could be adjusted with the concentration of corresponding ions, leading to programmable shape memory and shape recovery processes.
Asunto(s)
Resinas Acrílicas/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Polímeros/química , Resinas Acrílicas/síntesis química , Anisotropía , Iones/químicaRESUMEN
The present study was conducted to investigate the preventive effects of squid ink polysaccharides (SIP) on the damage of sperm and reproduction induced by cyclophosphamide that is most commonly used for treating clinically cancers. Male Kunming mice exposed to cyclophosphamide were administered with SIP and were sacrificed to determine sperm parameters, testicular antioxidant ability and reproductive capacity. Data indicated that cyclophosphamide caused obvious changes in mice such as significant reduction (P<0.01) of glutathione reductase activity (GR), vitamin C (Vc) content and total antioxidant capacity (T-AOC) in the testes, as well as elevation (P<0.01) of abnormal rates of sperm and fetus, and a decrease in the total fetal count and average fetal count (P<0.01), were totally alleviated by SIP. From these findings it can be concluded that SIP decreases chemotherapeutic damage to sperm and reproduction in mice induced by cyclophosphamide.