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The ventral subiculum (vSUB), the major output structure of the hippocampal formation, regulates motivation, stress integration, and anxiety-like behaviors that rely on heightened arousal. However, the roles and underlying neural circuits of the vSUB in wakefulness are poorly known. Using in vivo fiber photometry and multichannel electrophysiological recordings in mice, we found that the vSUB glutamatergic neurons exhibited high activities during wakefulness. Moreover, activation of vSUB glutamatergic neurons caused an increase in wakefulness and anxiety-like behaviors and induced a rapid transition from sleep to wakefulness. In addition, optogenetic stimulation of vSUB glutamatergic terminals and retrograde-targeted chemogenetic activation of vSUB glutamatergic neurons revealed that vSUB promoted arousal by innervating the lateral hypothalamus (LH), nucleus accumbens (NAc) shell, and prefrontal cortex (PFC). Nevertheless, local microinjection of dopamine D1 or D2/D3 receptor antagonist blocked the wake-promoting effect induced by chemogenetic activation of vSUB pathways. Finally, chemogenetic inhibition of vSUB glutamatergic neurons decreased arousal. Altogether, our findings reveal a prominent contribution of vSUB glutamatergic neurons to the control of wakefulness through several pathways.
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Hipocampo , Ratones Endogámicos C57BL , Vías Nerviosas , Optogenética , Vigilia , Animales , Vigilia/fisiología , Vigilia/efectos de los fármacos , Masculino , Ratones , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Vías Nerviosas/fisiología , Vías Nerviosas/efectos de los fármacos , Neuronas/fisiología , Neuronas/efectos de los fármacos , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiología , Ácido Glutámico/metabolismo , Ansiedad/fisiopatología , Nivel de Alerta/fisiología , Nivel de Alerta/efectos de los fármacosRESUMEN
This paper is devoted to the prescribed performance control (PPC) for a class of strict-feedback nonlinear systems with input saturation constraints. With the help of an improved tuning function, the system can achieve the desired steady-state and transient performance in the pre-designed time. A new error transformation function is introduced, which has inherent robustness, so it does not need to use any approximation technique or calculate the analytical derivative. Compared with the relevant results, the proposed scheme has the same lower complexity, but better transient and steady-state performance, although there exists uncertain nonlinearity and uncertain disturbances in the system. Finally, the correctness of the above algorithm is verified by simulation experiments.
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BACKGROUND: Accurate monitoring of tumor blood vessel normalization progression is beneficial to accurate treatment of patients. At present, there is a lack of safe and noninvasive monitoring methods. PURPOSE: To serial monitor the vascular normalization time window of tumor antiangiogenesis treatment through intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and histopathological methods. STUDY TYPE: Exploratory animal study. POPULATION: Sixty rat C6 glioma models were randomly and equally divided into the control groups (N = 30) and bevacizumab treatment groups (N = 30). Twenty-five for magnetic resonance imaging (MRI) and five for electron microscope testing in each group. FIELD STRENGTH/SEQUENCE: T1-weighted imaging (T1WI), T2WI with a fast spin echo sequence and IVIM-DWI with a spin-echo echo-planar imaging sequence at 3 T. ASSESSMENT: IVIM-DWI quantitative parameters (f, D, D*, and fD*) were obtained on days 0, 2, 4, 6, and 8 after bevacizumab treatment. After MRI, the microvessel density (MVD), pericyte coverage, and hypoxia-inducible factor-1α (HIF-1α) were assessed. Electron microscope observation was performed at each time point. STATISTICAL TESTS: One-way analysis of variance and Student's t-tests were used to compare differences within and between groups. Spearman's correlation coefficient (r) assess the correlation between IVIM and pathological parameters. The intragroup correlation coefficient was determined to assess the repeatability of each IVIM parameter. RESULTS: The IVIM-DWI perfusion parameters (f and fD*) of the treated group were higher than the control group on days 2 and 4. Compared to the control group, MVD decreased on days 2 and pericyte coverage increased on days 4 in the treatment group. Electron microscopy showed that the tight junctions of the treatment group were prolonged on days 2-4. In the control group, f had the highest correlation with MVD (r = 0.689). In the treated group, f had a good correlation with pericyte coverage (r = 0.557), HIF-1α had a moderately positive correlation with f (r = 0.480) and fD*(r = 0.447). DATA CONCLUSION: The vascular normalization time window of bevacizumab treatment of glioma was days 2-4 after antiangiogenesis treatment, which could be monitored noninvasively by IVIM-DWI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.
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Imagen de Difusión por Resonancia Magnética , Glioma , Animales , Bevacizumab/uso terapéutico , Imagen de Difusión por Resonancia Magnética/métodos , Glioma/diagnóstico por imagen , Glioma/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética/métodos , Movimiento (Física) , RatasRESUMEN
BACKGROUND: Although a number of studies have reported on the vascular abnormalities detected by magnetic resonance imaging (MRI) in patients with late-phase acute pancreatitis (AP), few have studied those occurring in the early phase of the disease. The aim of this research was to investigate the MRI findings of early vascular abnormalities in AP and to analyze the correlation of the prevalence of vascular involvement with the severity of AP based on the MR severity index (MRSI) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. METHODS: A retrospective analysis was conducted of 301 consecutive AP patients who were admitted to our institution between March 2013 and June 2019. All patients underwent initial MRI during the early phase of pancreatitis and one or more repeat MRI scans in the late phase. Peripancreatic vascular conditions and pancreatitis were assessed using T1-/T2-weighted imaging and dynamic-enhanced MRI. The association between the prevalence of vascular involvement and AP severity graded according to the MRSI or APACHE II score was analyzed using Spearman's rank correlation. RESULTS: Among 301 AP patients, 75 (24.9%) had at least one MRI-detected vascular abnormality. Overall, vascular involvement on MRI was higher in necrotizing pancreatitis than in edematous pancreatitis [43.2% (54/125) vs. 11.9% (21/176), χ2=38.2, P<0.001]. In the early phase of AP, the prevalence of splenic vein phlebitis, portal vein phlebitis, and splenic arterial arteritis was 24.9% (75/301), 22.3% (67/301), and 19.9% (60/301), respectively. Splenic vein phlebitis was seen on initial MRI in 55.6% (15/27) of patients who had splenic vein thrombosis on repeat MRI. The MRSI scores showed that the prevalence of splenic vein phlebitis, portal vein phlebitis, and splenic arterial arteritis, respectively, was correlated with the severity of pancreatitis (r=0.532, 0.487, and 0.456; all P<0.01). The APACHE II scores showed that the prevalence of MRI-detected vascular involvement was significantly correlated with AP severity (r=0.335, P<0.05). CONCLUSIONS: Vascular abnormalities, including splenic vein phlebitis and splenic arterial arteritis, are commonly seen on MRI in patients with early-phase AP, and they may be supplementary indicators that can reflect the severity of pancreatitis.
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To prove that ursolic acid(UA)could activate the autophagy of colorectal cancer HCT116 cells by inhibiting hedgehog signaling pathway. The effect of UA on the viability of HCT116 cells was determined by MTT assay. The effect of UA on the proliferation and migration of HCT116 cells was detected by crystal violet staining and scratch test. In the study on autophagy, the time points were screened out first: the autophagy fluorescence intensity of UA acting on HCT116 at different time points were detected by Cell Meter~(TM) Autophagy Assay Kit; Western blot was used to detect the expression of autophagy protein P62 at different time points. Then, Cell Meter~(TM) Autophagy Assay Kit was used to detect the effect of UA on autophagy fluorescence intensity of HCT116 cells. The effect of different doses of UA on the expressions of LC3â ¡ and P62 proteins in HCT116 cells were detected by Western blot. Further, AdPlus-mCherry-GFP-LC3 B adenovirus transfection was used to detect the effects of UA on autophagy flux of HCT116 cells; UA combined with autophagy inhibitor chloroquine(CQ) was used to detect the expression of LC3â ¡ by Western blot. In terms of mechanism, the effect of UA on hedgehog signaling pathway-related proteins in HCT116 cells was detected by Western blot. The results showed that UA inhibited the activity, proliferation and migration of HCT116 cells. UA enhanced the fluorescence intensity of autophagy in HCT116 cells, while promoting the expression of LC3â ¡ and inhibiting the expression of P62, in a time and dose dependent manner. UA activated the autophagy in HCT116 cells, which manifested that UA resulted in the accumulation of fluorescence spots and strengthened the fluorescence intensity of autophagosomes; compared with UA alone, UA combined with autophagy inhibitor CQ promoted the expression of LC3â ¡. UA reduced the expressions of PTCH1, GLI1, SMO, SHH and c-Myc in hedgehog signaling pathway, while increased the expression of Sufu. In conclusion, our study showed that UA activated autophagy in colorectal cancer HCT116 cells, which was related to the mechanism in inhibiting hedgehog signaling pathway activity.
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Neoplasias Colorrectales , Proteínas Hedgehog , Apoptosis , Autofagia , Línea Celular Tumoral , Proteínas Hedgehog/genética , Humanos , Transducción de Señal , Triterpenos , Ácido UrsólicoRESUMEN
Gliomas are one of the most common types of primary brain tumors. Despite recent advances in the combination of surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy) and supportive therapy in the multimodal treatment of gliomas, the overall prognosis remains poor and the longterm survival rate is low. Thus, it is crucial to develop a novel glioma management method. Due to its relatively noninvasive, selective and repeatable characteristics, photodynamic therapy (PDT) has been investigated for glioma therapy in the past decade, exhibiting higher selectivity and lower side effects compared with those of conventional therapy. However, most of the photosensitizers (PSs) are highly hydrophobic, leading to poor water solubility, rapid degradation with clearance in blood circulation and ultimately, low bioavailability. In the present study, hydrophilic polyethylene glycol (PEG)chlorin e6 (Ce6) chelated gadolinium ion (Gd3+) nanoparticles (PEGCe6Gd NPs) were synthesized via a chelation and selfassembly process. Initially, the cell cytotoxicity of PEGCe6Gd NPs was evaluated with or without laser irradiation. The in vitro study demonstrated the lack of toxicity of PEGCe6Gd NPs to tumor cells in the absence of laser irradiation. However, its toxicity was enhanced under laser irradiation. Moreover, the size and weight of brain tumors were significantly decreased in mice with glioma xenografts, which was further confirmed via histological analysis. Subsequently, the results indicated that the PEGCe6Gd NPs had a favorable T1weighted contrast performance (0.43 mg ml1 s1) and were observed to have signiï¬cant contrast enhancement at the tumor site from 0.25 to 1 h postinjection in vivo. The favorable MRI, as well as the synergetic photodynamic antitumor effect and antineoplastic ability of PEGCe6Gd NPs was identified. It was suggested that PEGCe6Gd NPs had great potential in the diagnosis and PDT treatment of gliomas, and possibly other cancer types, with prospects of clinical application in the near future.
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Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Nanopartículas Multifuncionales/administración & dosificación , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Línea Celular Tumoral/trasplante , Clorofilidas , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Gadolinio/administración & dosificación , Gadolinio/química , Glioma/diagnóstico por imagen , Glioma/patología , Humanos , Imagen por Resonancia Magnética Intervencional , Ratones , Nanopartículas Multifuncionales/química , Fármacos Fotosensibilizantes/química , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Porfirinas/administración & dosificación , Porfirinas/química , RatasRESUMEN
OBJECTIVE: This study aimed to quantitatively evaluate the left ventricular myocardial work of patients with chronic kidney disease (CKD) by echocardiographic pressure-strain loop (PSL) analysis. METHODS: Ninety-three patients with CKD and forty-two age- and sex-matched controls were included in the study. CKD patients were divided into group 1 (stages 2-4) and group 2 (stage 5). Left ventricular blood pressure was estimated noninvasively according to echocardiographic valvular events and brachial artery systolic pressure. Left ventricular myocardial work parameters were acquired by echocardiographic PSL analysis. RESULTS: The CKD groups had a significantly lower global work index (WI), global work efficiency (GWE), global constructive strain (GCW) and global longitudinal strain (GLS) and higher global waste work (GWW) than the control group. Segmental analysis showed that the myocardial WI, work efficiency (WE), and constructive work (CW) were lower in group 2 than the control group (P < .05), while the regional myocardial waste work (WW) was higher (P < .05). A Pearson correlation analysis revealed that GWE and GWW have good correlations with the LVEF and GLS. A multiple regression analysis showed that the systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), end-diastolic volume (EDV), and GLS were associated with global work index (GWI) (b' = 0.476, 0.252, -0.407, and -0.355, P < .05). CONCLUSIONS: Left ventricular PSL analysis can be applied to assess global and regional myocardial work in CKD patients. This approach may serve as a noninvasive method for the detection of left ventricular systolic dysfunction at an early stage.
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Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Ecocardiografía , Humanos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico por imagen , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular IzquierdaRESUMEN
The objective of this study was to investigate the inhibitory effect of scutellarin on the differentiation of colonic cancer stem cells in vitro and in vivo and to explore its underlying hedgehog signaling-based mechanism. The effect of scutellarin on the growth in vitro of HT-29 cells-derived cancer stem-like cells(HT-29 CSC) was observed with 3 D cell culture. The effect of scutellarin on the transformation of HT-29 CSC cells was assessed by soft agar colony formation assay. Fetal calf serum was used to induce differentiation of stem cells and observe the effect of scutellarin on HT-29 CSC cells differentiation in vitro. The effects of scutellarin on mRNA expressions of Lgr5, c-Myc, CK20 and Nanog in HT-29 CSC cells were determined by quantitative Real-time polymerase chain reaction(qRT-PCR). The effects of scutellarin on protein expressions of c-Myc, Gli1 and Lgr5 in HT-29 CSC cells were examined by Western blot. After subcutaneous implantation of HT-29 CSC cells in nude mice, the effect of scutellarin on the mouse body weight and the growth of HT-29 CSC-derived tumor were explored. qRT-PCR was used for evaluating the effect of scutellarin on mRNA levels of CD133, Lgr5, Gli1, Ptch1, c-Myc, Ki-67, CK20 and Nanog in tumor. Western blot and immunohistochemistry analysis were used to detect the effect of scutellarin on protein expressions of c-Myc, Gli1, Lgr5, CD133 and Ki-67 in tumor. The in vitro experiments showed that scutellarin inhibited the growth, transformation and differentiation of HT-29 CSC cells, significantly down-regulated the mRNA levels of Lgr5, c-Myc, CK20 and Nanog in HT-29 CSC cells as well as the protein expression levels of c-Myc, Gli1 and Lgr5 in HT-29 CSC cells. Additionally, animal experiments showed that scutellarin significantly inhibited the growth of subcutaneous xenografts in nude mice, and down-regulated the mRNA expressions of CD133, Lgr5, Gli1, Ptch1, c-Myc, Ki-67, CK20 and Nanog as well as the protein levels of c-Myc, Gli1, Lgr5, CD133 and Ki-67 of xenografts in nude mice. Taken together, scutellarin could inhibit the differentiation of colo-nic cancer stem cells in vitro and in vivo, potentially by down regulation of hedgehog signaling pathway activity.
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Células Madre Neoplásicas , Animales , Apigenina , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Glucuronatos , Proteínas Hedgehog , Humanos , Ratones , Ratones DesnudosRESUMEN
BACKGROUND: The remarkable abilities of the human brain are distinctive features that set us apart from other animals. However, our understanding of how the brain has changed in the human lineage remains incomplete, but is essential for understanding cognition, behavior, and brain disorders in humans. Here, we compared the expression trajectory in brain development between humans and rhesus macaques (Macaca mulatta) to explore their divergent transcriptome profiles. RESULTS: Results showed that brain development could be divided into two stages, with a demarcation date in a range between 25 and 26 postconception weeks (PCW) for humans and 17-23PCWfor rhesus macaques, rather than birth time that have been widely used as a uniform demarcation time of neurodevelopment across species. Dynamic network biomarker (DNB) analysis revealed that the two demarcation dates were transition phases during brain development, after which the brain transcriptome profiles underwent critical transitions characterized by highly fluctuating DNB molecules. We also found that changes between early and later brain developmental stages (as defined by the demarcation points) were substantially greater in the human brain than in the macaque brain. To explore the molecular mechanism underlying prolonged timing during early human brain development, we carried out expression heterochrony tests. Results demonstrated that compared to macaques, more heterochronic genes exhibited neoteny during early human brain development, consistent with the delayed demarcation time in the human lineage, and proving that neoteny in human brain development could be traced to the prenatal period. We further constructed transcriptional networks to explore the profile of early human brain development and identified the hub gene RBFOX1 as playing an important role in regulating early brain development. We also found RBFOX1 evolved rapidly in its non-coding regions, indicating that this gene played an important role in human brain evolution. Our findings provide evidence that RBFOX1 is a likely key hub gene in early human brain development and evolution. CONCLUSIONS: By comparing gene expression profiles between humans and macaques, we found divergent expression trajectories between the two species, which deepens our understanding of the evolution of the human brain.
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Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Evolución Molecular , Regulación del Desarrollo de la Expresión Génica , Animales , Redes Reguladoras de Genes , Humanos , Macaca mulatta/genética , Macaca mulatta/crecimiento & desarrollo , Especificidad de la Especie , TranscriptomaRESUMEN
BACKGROUND Artemisia annua exerts powerful effects in non-small cell lung carcinoma (NSCLC). Some studies have shown that Artemisia annua possesses the characteristics of new therapeutic drugs for NSCLC patients. However, the underlying molecular mechanism of Artemisia annua anti-NSCLC is not yet fully elucidated because Artemisia annua contains hundreds of ingredients. This study aimed to conduct network pharmacological analysis on the mechanism of action of Artemisia annua against NSCLC. MATERIAL AND METHODS The active ingredients and corresponding potential targets of Artemisia annua were searched and screened in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then through The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) databases to establish NSCLC related targets. Based on the matching results of Artemisia annua potential targets and NSCLC targets, a protein-protein interaction (PPI) network was constructed to analyze the interactions between these targets and topologically screen the central targets. Furthermore, Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment were carried out. RESULTS There were 19 main active ingredients of Artemisia annua screened for target prediction; 40 NSCLC-related common targets were identified via multiple NSCLC databases. The node area and corresponding degree value of AKT1, MYC, CCND1, VEGFA, JUN, MAPK1, EGFR, and ESR1 were large and could be easily found in the PPI network. The aforementioned results were further verified by the analysis of GO biological function and KEGG enrichment analysis. CONCLUSIONS The network pharmacology analysis reveals the molecular biological mechanism of Artemisia annua anti-NSCLC via multiple active components, multi-channels, and multi-targets. This suggests that Artemisia annua might be developed as a promising anti-NSCLC drug.
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Artemisia annua/química , Artemisia annua/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , China , Bases de Datos Factuales , Bases de Datos Genéticas , Medicamentos Herbarios Chinos/farmacología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Medicina Tradicional China/métodos , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología , Mapas de Interacción de Proteínas , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To determine the characteristics of type 2 diabetes mellitus (T2DM)-related acute pancreatitis (AP) on magnetic resonance imaging (MRI). METHODS: Retrospectively studied 262 patients with AP were admitted to our institution and underwent MRI. Diagnosis of T2DM-related AP was based on clinical manifestations, laboratory tests, and MRI. Pancreatic/peripancreatic changes were assessed on MRI. RESULTS: Fifty-three (20.2%) patients with T2DM-related AP and 209 (79.8%) with nondiabetic AP were enrolled. On MRI, a higher prevalence of necrotizing pancreatitis (P < 0.001), pancreatic necrosis >30% (57.5% vs 29.2%; P = 0.006), hemorrhage (35.8% vs 19.1%; P = 0.009), abdominal wall edema (67.9% vs 46.8%; P = 0.006), walled-off necrosis (43.2% vs 14.6%; P < 0.001), and infected collections (P < 0.001) were registered in T2DM with AP. T2DM-related AP sustained greater magnetic resonance severity index (mean, 5.1 [range, 2-10] vs 3.4 [range, 1-10]; P < 0.001), higher incidence of moderate and severe pancreatitis (69.8% vs 40.2%; P < 0.001), higher organ failure (45.3% vs 22%; P = 0.001), and prolonged hospitalization (mean, 25.2 [range, 10-63] vs 16 [range, 5-48] days; P < 0.001). CONCLUSIONS: Type 2 diabetes mellitus-related AP is more moderate-to-severe pancreatitis, and it correlates with MRI characteristics of the pancreas itself, hemorrhage, abdominal wall, and infected collections.
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Diabetes Mellitus Tipo 2/complicaciones , Imagen por Resonancia Magnética , Pancreatitis/etiología , Adulto , Anciano , Glucemia/análisis , Comorbilidad , Diabetes Mellitus Tipo 2/sangre , Edema/etiología , Femenino , Hemorragia/etiología , Hospitalización , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/etiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Método Simple Ciego , Tomografía Computarizada por Rayos X , Adulto JovenAsunto(s)
Infecciones por Coronavirus/fisiopatología , Neumonía Viral/fisiopatología , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anemia/sangre , Anemia/fisiopatología , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus , COVID-19 , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Comorbilidad , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Tos/fisiopatología , Diabetes Mellitus/epidemiología , Diarrea/fisiopatología , Combinación de Medicamentos , Fatiga/fisiopatología , Femenino , Fiebre/fisiopatología , Productos de Degradación de Fibrina-Fibrinógeno , Hospitalización/estadística & datos numéricos , Humanos , Hipertensión/epidemiología , Recuento de Leucocitos , Leucocitosis/sangre , Leucocitosis/fisiopatología , Leucopenia/sangre , Leucopenia/fisiopatología , Lopinavir/uso terapéutico , Pulmón/diagnóstico por imagen , Recuento de Linfocitos , Linfopenia/sangre , Linfopenia/fisiopatología , Masculino , Persona de Mediana Edad , Mialgia/fisiopatología , Neoplasias/epidemiología , Neutrófilos , Ventilación no Invasiva , Terapia por Inhalación de Oxígeno , Pandemias , Neumonía Viral/sangre , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Polipéptido alfa Relacionado con Calcitonina/sangre , Respiración Artificial , Estudios RetrospectivosRESUMEN
In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
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Betacoronavirus , Infecciones por Coronavirus , Infección Hospitalaria , Control de Infecciones , Tamizaje Masivo , Equipo de Protección Personal , Neumonía Viral , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/aislamiento & purificación , Betacoronavirus/patogenicidad , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Infección Hospitalaria/prevención & control , Diagnóstico Diferencial , Medicamentos Herbarios Chinos , Medicina Basada en la Evidencia , Fluidoterapia , Humanos , Control de Infecciones/normas , Pulmón/diagnóstico por imagen , Epidemiología Molecular , Atención de Enfermería , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/etiología , Neumonía Viral/terapia , Neumonía Viral/transmisión , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19RESUMEN
The mutation status of KRAS is a significant biomarker in the prognosis of rectal cancer. This study investigated the feasibility of MRI-based radiomics in predicting the mutation status of KRAS with a composite index which could be an important criterion for KRAS mutation in clinical practice. In this retrospective study, a total of 127 patients with rectal cancer were enrolled. The 3D Slicer was used to extract the radiomics features from the MRI images, and sparse support vector machine (SVM) with linear kernel was applied for feature reduction. The radiomics classifier for predicting the KRAS status was then constructed by Linear Discriminant Analysis (LDA) and its performance was evaluated. The composite index was determined with LDA model. Out of 127 rectal cancer subjects, there were 44 KRAS mutation cases and 83 wild cases. A total of 104 radiomics features were extracted, 54 features were filtered by linear SVM with L1-norm regularization and 6 features that had no significant correlations within them were finally selected. The radiomics classifier constructed using the 6 features featured an AUC value of 0.669 (specificity: 0.506; sensitivity: 0.773) with LDA. Furthermore, the composite index (Radscore) had statistically significant difference between the KRAS mutation and wild groups. It is suggested that the MRI-based radiomics has the potential in predicting the KRAS status in patients with rectal cancer, which may enhance the diagnostic value of MRI in rectal cancer.
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Imagen por Resonancia Magnética/métodos , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias del Recto/diagnóstico por imagen , Adulto , Anciano , Análisis Discriminante , Detección Precoz del Cáncer , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Recto/genética , Estudios Retrospectivos , Sensibilidad y Especificidad , Máquina de Vectores de Soporte , Adulto JovenRESUMEN
To assess the duct-road sign and tumor-to-duct ratio (TDR) in MRI for differentiating pancreatic neuroendocrine tumors (PNETs) from pancreatic ductal-adenocarcinomas (PDACs).Retrospectively reviewed MRI characteristics of 78 pancreatic masses (histopathology-proven 25 PNETs and 53 PDACs). Receiver operating characteristics with TDR and diagnostic performance of the duct-road sign for differential diagnosis were performed.The prevalence of duct-road sign in PNETs was higher than that for PDACs (84% vs 0%; Pâ<â.001). A strong correlation (râ=â0.884, Pâ<â.001) was observed between MRI for PNETs and the frequency of this sign. Performance characteristics of the duct-road sign in MRI for PNET diagnosis were sensitivity (84%, [21 of 25]), specificity (100%, [53 of 53]), positive predictive value (100%, [21 of 21]), negative predictive value (92.9%, [53 of 57]), and accuracy (94.8%, [74 of 78]). In the intention-to-diagnose analysis, the corresponding values were 67.7% (21 of 31), 100% (53 of 53), 100% (21 of 21), 84.1% (53 of 63), and 88.1% (74 of 84). The TDR in PNETs was observed to be greater than that in PDACs (14.6â±â9.3 vs 6.9â±â3.8, Pâ=â.001). TDR with a cut-off value of 7.7 had high sensitivity (84%) and specificity (66%) with area under curve (0.802, 95% CI: 0.699, 0.904; Pâ<â.001) for distinguishing PNETs from PDACs.The presence of duct-road sign and TDR > 7.7 on MRI may assist in diagnosis for PNET instead of PDAC.
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Adenocarcinoma/patología , Tumores Neuroendocrinos/patología , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Adenocarcinoma/diagnóstico por imagen , Adulto , Anciano , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/patología , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Conductos Pancreáticos/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Reproducibilidad de los Resultados , Estudios Retrospectivos , Carga TumoralRESUMEN
Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1â¯mg/mL) increased to 70⯰C under near-infrared light irradiation within 4â¯min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo. In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808â¯nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.
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Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine which controls the differentiation and growth of hematopoietic cells in the bone marrow. We report a severe aplastic anemia (SAA) patient with false-negative 99mTc sodium phytate bone marrow imaging findings under concurrent G-CSF therapy. The first bone marrow imaging showed a normal bone marrow activity. However, the bone marrow biopsy pathology report revealed a lack of hematopoietic cells. Furthermore, the complete blood count indicated severe pancytopenia resulting in the diagnosis of aplastic anemia (AA). A second marrow scan implemented after the stoppage of G-CSF showed an abnormal bone marrow activity, which matched the pathology reports. Accordingly, the concurrent administration of G-CSF was considered as the cause of false-negative bone marrow imaging findings obtained in the first scan. Consequently, it should be kept in mind that a 99mTc sodium phytate bone marrow scintigraphy during the concurrent administration of G-CSF may lead to the achievement of false negative results because it induces changes in bone marrow mimicking a normal marrow scan in patients with AA.
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Acute pancreatitis is classically characterized by acute chemical inflammation of the pancreatic gland itself, peripancreatic tissues, and even remote organs. The newly revised Atlanta Classification 2012 redefined the patterns of pancreatic necrosis and local complications in acute pancreatitis. The Atlanta Classification's novelty was in emphasizing that extrapancreatic fat necrosis, which leads to walled-off necrosis, is associated with poor prognosis. Conversely, the free fluid liquid was considered to be less related to complications. The Atlanta's classification's main weakness is that it is mainly computed tomography (CT) based, as contrast-enhanced CT is the predominant imaging technique used for evaluating a wide range of pathological processes of acute pancreatitis. However, some local complications are difficult to distinguish accurately on CT. Recent advances, including significantly better soft-tissue contrast, favor multiparametric magnetic resonance imaging (mpMRI) for a more comprehensive assessment of acute pancreatitis pathology, particularly for small necrotic/fat debris within a collection. In addition, the MRI severity index (MRSI), which combines Balthazar's grade points and points of the extent of pancreatic necrosis, has been proven to be crucial for the initial evaluation, staging, and prognosis of acute pancreatitis. Other innovations, such as the recognition of important MRI features in acute pancreatitis and the utilization of newer, more effective terminology for imaging reporting assistance in the differentiation of the common local complications following this disease, have improved the treatment for acute pancreatitis. In this paper, with reference to the 2012 revised Atlanta classification, we review the strengths and limitations of MRI for identifying acute pancreatitis, the MRI findings of a spectrum of pathological entities, and the important local complications secondary to acute pancreatitis.
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Multifunctional nanomaterials with simple structure and good biosafety, integrating multimodal imaging and therapeutic functions, can facilitate the development of clinical cancer treatments. Here, a simple but powerful pure bismuth based nanoparticle (Gd-PEG-Bi NPs) was developed from pure Bi NPs and gadolinium-diethylenetriaminepentaacetic acid-bis-tetradecylamide, which not only shows high quality MRI/CT/PAI triple-modal imaging, but can also be a potent photothermal therapy agent under the guidance of the triple-modal imaging. The Gd-PEG-Bi NPs showed good stability and excellent biocompatibility. In vitro and in vivo study demonstrated that Gd-PEG-Bi NPs have ultrahigh X-ray attenuation coefficient, short T1 relaxation time in MRI, and strong PAI signal. Following the imaging diagnosis, the excellent light-to-heat conversion efficiency of Gd-PEG-Bi NPs was capable of suppressing the tumor growth effectively under near-infrared laser radiation in vivo. Such multifunctional nanoparticles were ideal candidates for cancer diagnosis and treatment.
Asunto(s)
Bismuto/química , Medios de Contraste/química , Gadolinio/química , Imagen por Resonancia Magnética/métodos , Imagen Multimodal/métodos , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animales , Femenino , Hemólisis , Ratones , Ratones Endogámicos BALB C , Ácido Pentético/análogos & derivados , Ácido Pentético/químicaRESUMEN
New genes are drivers of evolutionary innovation and phenotypic evolution. Expression of new genes in early development raises the possibility that new genes could originate and be recruited for functions in embryonic development, but this remains undocumented. Here, based on temporal gene expression at different developmental stages in Xenopus tropicalis, we found that young protein-coding genes were significantly enriched for expression in developmental stages occurring after the midblastula transition (MBT), and displayed a decreasing trend in abundance in the subsequent stages after MBT. To complement the finding, we demonstrate essential functional attributes of a young orphan gene, named as Fog2, in morphological development. Our data indicate that new genes could originate after MBT and be recruited for functions in embryonic development, and thus provide insights for better understanding of the origin, evolution, and function of new genes.