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We present a space-angle dual multiplexing holographic recording system for realizing single-exposure multi-wavelength optical diffraction tomographic (ODT) imaging. This system is achieved by combining the principle of single-exposure multi-wavelength holographic imaging technique based on angle-division multiplexing with the principle of single-exposure ODT imaging technique based on microlens array multi-angle illuminations and space-division multiplexing. Compared with the existing multi-wavelength ODT imaging methods, it enables the holographic recording of all the diffraction tomography information of a measured specimen at multiple illumination wavelengths in a single camera exposure without any scan mechanism. Using our proposed data processing method, the multi-wavelength three-dimensional (3D) refractive index tomograms of a specimen can be eventually reconstructed from single recorded multiplexing hologram. Experimental results of a static polystyrene bead and a living C. elegans worm demonstrate the feasibility of this system.
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Background: In this study, we investigated the prediction and prognostic value of SDF-1 for triple-negative breast cancer (TNBC) patients who underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. Methods: A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. SDF-1 and CXCR4 expression were measured at baseline and surgery via enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. Results: Of the 303 patients, 103 (34.0%) experienced pathological complete response (pCR) after completion of NAC. Serum SDF-1 expression before NAC was significantly correlated with the abundance of TILs. A higher pCR rate was more likely to be observed in patients with lower serum SDF-1 levels before NAC (P=0.001, OR=0.997, 95% CI: 0.996-0.999) and higher levels of TILs (P=0.005). In the multivariate survival model for nonpCR patients, serum SDF-1 expression at surgery served as an independent prognostic value for survival (high level, HR=1.980, 95% CI: 1.170-3.350, low level was used as a reference; P=0.011). Additionally, the predictive and prognostic value of serum SDF-1 expression was significant in patients with high abundance of TILs but not in patients with low abundance of TILs. Conclusions: This study contributes to the clarification of the value of serum SDF-1 to predict pCR and survival for TNBC patients who underwent NAC. This new serum marker, together with TILs, might help identify clinical subtypes of TNBC with different treatment responses and survival and play an important role in tailoring and modifying the NAC strategy for advanced TNBCs in the future.
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Terapia Neoadyuvante , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/metabolismo , Linfocitos Infiltrantes de Tumor/metabolismo , Pronóstico , InmunohistoquímicaRESUMEN
Cells of the aerobic metabolic organism are inevitably subjected to the damage from reactive oxygen species (ROS). ROS cause multiple forms of DNA damage, among which the oxidation product of guanine G 8-hydroxyguanine (8-oxoG) is the most frequent DNA oxidative damage, recognized by the specific glycosidase OGG1 that initiates the base excision repair pathway. If left unrepaired, 8-oxoG may pair with A instead of C, leading to a mutation of G: C to T: A during replication. Thus, the accumulation of 8-oxoG or the abnormal OGG1 repair is thought to affect gene function, which in turn leads to the development of tumor or aging-related diseases. However, a series of recent studies have shown that 8-oxoG tends to be produced in regulatory regions of the genome. 8-oxoG can be regarded as an epigenetic modification, while OGG1 is a specific reader of this information. Substrate recognition, binding or resection by OGG1 can cause DNA conformation changes or affect histone modifications, causing up-regulation or down-regulation of genes with different properties. Thus, in addition to the potential genotoxicity, the association of guanine oxidative damage with development of tumors is closely related to its aberrant initiation of gene expression through epigenetic mechanisms. In this review, we summarize the underlying mechanism of 8-oxoG and repair enzyme OGG1 in tumor development and progression, with aims to interpret the relationship between DNA oxidative damage and tumor from a new perspective, and provide new ideas and targets for tumor treatment.
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ADN Glicosilasas , Neoplasias , ADN , Daño del ADN , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismo , Reparación del ADN , Guanina/análogos & derivados , Guanina/metabolismo , Humanos , Neoplasias/genética , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: In contrast to many Western countries, China has maintained its large psychiatric hospitals. The prevalence and clinical characteristics of coronavirus disease 2019 (COVID-19) in inpatients with schizophrenia (SCZ) are unclear. AIM: To assess the prevalence of COVID-19 among inpatients with SCZ and compare the infected to uninfected SCZ patients in a Wuhan psychiatric hospital. METHODS: We retrospectively collected demographic characteristics and clinical profiles of all SCZ patients with COVID-19 at Wuhan's Youfu Hospital. RESULTS: Among the 504 SCZ patients, 84 had COVID-19, and we randomly sampled 174 who were uninfected as a comparison group. The overall prevalence of COVID-19 in SCZ patients was 16.7%. Among the 84 SCZ patients with confirmed COVID-19, the median age was 54 years and 76.2% were male. The most common symptom was fever (82%), and less common symptoms were cough (31%), poor appetite (20%), and fatigue (16%). Compared with SCZ patients without COVID-19, those with COVID-19 were older (P = 0.006) and significantly lighter (P = 0.002), and had more comorbid physical diseases (P = 0.001). Surprisingly, those infected were less likely to be smokers (< 0.001) or to be treated with clozapine (P = 0.03). Further logistic regression showed that smoking [odds ratio (OR) = 5.61], clozapine treated (OR = 2.95), and male (OR = 3.48) patients with relatively fewer comorbid physical diseases (OR = 0.098) were at a lower risk for COVID-19. SCZ patients with COVID-19 presented primarily with fever, but only one-third had a cough, which might otherwise be the most common mode of transmission between individuals. CONCLUSION: Two unexpected protective factors for COVID-19 among SCZ inpatients are smoking and clozapine treatment.
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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused major public panic in China. Pregnant women may be more vulnerable to stress, which may cause them to have psychological problems. AIM: To explore the effects of perceived family support on psychological distress in pregnant women during the COVID-19 pandemic. METHODS: A total of 2232 subjects were recruited from three cities in China. Through the online surveys, information on demographic data and health status during pregnancy were collected. Insomnia severity index, generalized anxiety disorder 7-item scale, patient health questionnaire-9, somatization subscale of the symptom check list 90 scale, and posttraumatic stress disorder checklist were used to assess the psychological distress. RESULTS: A total of 1015 (45.4%) women reported having at least one psychological distress. The women who reported having inadequate family support were more likely to suffer from multiple psychological distress (≥ 2 psychological distress) than women who received adequate family support. Among the women who reported less family support, 41.8% reported depression, 31.1% reported anxiety, 8.2% reported insomnia, 13.3% reported somatization and 8.9% reported posttraumatic stress disorder (PTSD), which were significantly higher than those who received strong family support. Perceived family support level was negatively correlated with depressive symptoms (r = -0.118, P < 0.001), anxiety symptoms (r = -0.111, P < 0.001), and PTSD symptoms (r = -0.155, P < 0.001). CONCLUSION: Family support plays an important part on pregnant women's mental health during the COVID-19 pandemic. Better family support can help improve the mental health of pregnant women.
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BACKGROUND: In this study we investigate the prediction and prognostic value of CXCL8-CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery. METHODS: A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation. RESULTS: Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2- patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery (P = 0.004, HR 0.939, 95% CI 0.900-0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933-4.949; CXCR1/2++, HR 3.466, 95% CI 1.569-7.655, CXCR1/2- was used as a reference; P = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome. CONCLUSIONS: This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8-CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Interleucina-8/metabolismo , Terapia Neoadyuvante/mortalidad , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8B/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Carboplatino/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Proyectos Piloto , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
BACKGROUND: This study aimed to investigate the clinical utility of serum biomarker changes during neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). METHODS: A total of 303 patients with TNBC were included in this study. Serum samples were taken at three time points during NAC: baseline, prior to the third cycle, and prior to surgery. Luminex multibiomarker panel for 29 serum biomarkers was used to detect their correlation with NAC response. The predictive and prognostic value of each selected biomarker was then studied. RESULTS: Vascular endothelial growth factor (VEGF) was the only biomarker that correlated with treatment response, with a decreasing trend in pCR patients relative to non-pCR patients (p < .001). Univariable and multivariable analyses revealed that the relative change in VEGF prior to the third cycle of NAC had a remarkable predictive value for both pCR and pathological nonresponse with high sensitivity and specificity. VEGF was also independently correlated with disease-free survival. CONCLUSION: Our findings indicate that monitoring serum VEGF could help identify patients with different responses at an early time point of NAC and at varying risk of disease relapse. Serum VEGF may also serve as an alternative to traditional response-evaluating methodologies in tailoring and modifying the NAC strategy for both operable and advanced TNBCs. IMPLICATIONS FOR PRACTICE: Neoadjuvant chemotherapy (NAC) followed by definitive surgery is a standard of care for locally advanced breast cancer. The identification of sensitive responders to neoadjuvant therapy is highly significant for breast cancer, especially triple-negative breast cancer (TNBC). Results of this study indicate that the monitoring of serum vascular endothelial growth factor (VEGF) could identify patients with favorable or poor responses at an early time point of NAC. Furthermore, the prediction power of VEGF was better than traditional response-evaluating methods. VEGF might serve as a complement or alternative to traditional imaging-based response-evaluating methodologies in tailoring systemic treatment strategies for both operable and advanced TNBCs.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama Triple Negativas/terapia , Factor A de Crecimiento Endotelial Vascular/sangre , Adulto , Supervivencia sin Enfermedad , Monitoreo de Drogas/métodos , Estudios de Factibilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Mastectomía , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Selección de Paciente , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Neoplasias de la Mama Triple Negativas/sangre , Neoplasias de la Mama Triple Negativas/mortalidadRESUMEN
BACKGROUND: Triple-negative breast cancers (TNBCs) are initially responsive to chemotherapy, but most recurrent TNBCs develop resistance. Autophagy is believed to play dual roles in cancer and might contribute to chemoresistance. In this study, we aimed to investigate the role of autophagy and its regulator, eukaryotic elongation factor 2 kinase (eEF2K), in determining the biological nature of TNBC. METHODS: We used in vitro models of TNBC, namely, paclitaxel-resistant cell lines derived from sensitive cell lines. Various approaches to measuring autophagy flux were applied. We assessed the effects of inhibiting autophagy and silencing eEF2K on cell viability, tumor formation and invasion. We also collected residual tumor samples from 222 breast cancer patients who underwent neoadjuvant chemotherapy and measured eEF2K and LC3 expression levels by immunohistochemistry (IHC). Multivariate survival analysis was used to determine prognostic variables. RESULTS: Compared to the parental lines, the chemoresistant lines exhibited enhanced starvation-stimulated autophagy and showed significant decreases in cell viability, growth and invasion upon treatment with autophagy inhibitors. eEF2K silencing also resulted in the suppression of autophagic activity and in aggressive biological behavior. In the survival analysis, residual tumor LC3 (P=0.001) and eEF2K (P=0.027) expression levels were independent prognostic factors for patients who underwent neoadjuvant chemotherapy, especially in those with TNBC. CONCLUSIONS: Our study indicated that eEF2K and autophagy play key roles in the maintenance of aggressive tumor behavior and chemoresistance in resistant TNBC. eEF2K silencing may be a novel strategy for the treatment of TNBC.
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BACKGROUND: This study aimed to investigate the clinical utility of serum and histological MMP-9 detection during neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC). METHODS: A total of 303 TNBC patients who underwent weekly paclitaxel plus carboplatin treatments followed by surgical resection were included in this study. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum level of Matrix metalloproteinase-9 (sMMP-9) at baseline and prior to surgery. Immunohistochemistry was used to detect histological MMP-9 (hMMP-9) expression in patients with residual tumors after NAC. The value of MMP-9 to predict the response to NAC and patient survival was studied. RESULTS: Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. Univariate and multivariate analyses revealed that the relative change in sMMP-9, rather than sMMP-9 at baseline or surgery, had a remarkable predictive value for pCR. Each 1 ng/ml decrease in sMMP-9 after NAC was shown to result in a 0.3% increase in pCR rate. Additionally, in survival analyses, hMMP-9 expression in residual tumors was independently correlated with disease-free survival for non-pCR responders (P < 0.001). CONCLUSIONS: Our findings indicate that monitoring serum MMP-9 and detection of histological MMP-9 could help identify TNBC patients who will respond to NAC and will display varying risks of disease relapse. MMP-9 may serve as a predictive and prognostic biomarker for tailoring and modifying the NAC strategy for TNBC.
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Metaloproteinasa 9 de la Matriz/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/mortalidad , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Quimioterapia Adyuvante , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Metaloproteinasa 9 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/genética , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Adulto JovenRESUMEN
Paroxysmal kinesigenic dyskinesia (PKD) is a heterogeneous movement disorder characterized by recurrent dyskinesia attacks triggered by sudden movement. PRRT2 has been identified as the first causative gene of PKD. However, it is only responsible for approximately half of affected individuals, indicating that other loci are most likely involved in the etiology of this disorder. To explore the underlying causative gene of PRRT2-negative PKD, we used a combination strategy including linkage analysis, whole-exome sequencing and copy number variations analysis to detect the genetic variants within a family with PKD. We identified a linkage locus on chromosome 12 (12p13.32-12p12.3) and detected a novel heterozygous mutation c.956 T>G (p.319 L>R) in the potassium voltage-gated channel subfamily A member 1, KCNA1. Whole-exome sequencing in another 58 Chinese patients with PKD who lacked mutations in PRRT2 revealed another novel mutation in the KCNA1 gene [c.765 C>A (p.255 N>K)] within another family. Biochemical analysis revealed that the L319R mutant accelerated protein degradation via the proteasome pathway and disrupted membrane expression of the Kv1.1 channel. Electrophysiological examinations in transfected HEK293 cells showed that both the L319R and N255K mutants resulted in reduced potassium currents and respective altered gating properties, with a dominant negative effect on the Kv1.1 wild-type channel. Our study suggests that these mutations in KCNA1 cause the Kv1.1 channel dysfunction, which leads to familial PKD. The current study further extended the genotypic spectrum of this disorder, indicating that Kv1.1 channel dysfunction maybe one of the underlying defects in PKD.
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Distonía/genética , Canal de Potasio Kv.1.1/genética , Adulto , Pueblo Asiatico , Variaciones en el Número de Copia de ADN , Femenino , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , LinajeRESUMEN
Township and Village Health Services Integration Management (TVHSIM) is an essential form of China's two-tiered health service integration plan at the township and village level. Its main purpose, also one of the target goals in China's new healthcare reform, is to gradually integrate rural health services and appropriately allocate rural health resources. This study aims to assess the village doctors' satisfaction with the TVHSIM and provide scientific base to further improve TVHSIM. A cross-sectional study was carried out in which 162 village doctors from Qinghai, Inner Mongolia and Xinjiang in western China were interviewed. Descriptive analysis, independent t-test, one-way ANOVA, Spearman rank correlation and multiple linear regression were used to analyze the difference and relevance between village doctors' personal characteristics and their satisfaction with TVHSIM and six subscales. Village doctors with different years of practice, social insurance status and essential medical knowledge level showed statistically significant differences in their satisfaction levels (all P<0.05). Age (P<0.05) and years of practice (P<0.01) were negatively correlated with Drug and Medical Device Management and Financing Management. Essential medical knowledge level (P<0.05) was negatively correlated with Operations Management as well. However, social insurance status (P<0.05) was positively correlated with Human Resources Management and Drug and Medical Device management. Gender, age and years of practice respectively had significant influence on village doctors' satisfaction with TVHSIM (P<0.01). In conclusion, in order to further promote TVHSIM policy in rural China, a well-rounded social insurance model for village doctors is urgently needed. In addition, the development of TVHSIM is regionally imbalanced. Efficient and effective measures aiming at rationalizing gender and age structure and enhancing essential medical training should be carefully considered.
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Médicos/psicología , Servicios de Salud Rural/normas , Salud Rural/normas , Adulto , Anciano , China/etnología , Estudios Transversales , Femenino , Accesibilidad a los Servicios de Salud/normas , Humanos , Masculino , Persona de Mediana Edad , Satisfacción Personal , Factores Socioeconómicos , Adulto JovenRESUMEN
This study sought to investigate the prevalence of programmed death ligand 1 (PD-L1) and its prognostic value in patients with residual tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer. A total of 309 patients considered as non-pathological complete responders (non-pCR) after NCT followed by mastectomy were selected. The expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens. The median density was used to classify PD-L1 expression from low to high. The prognostic value of various clinicopathological factors was evaluated. The expression of PD-L1 was more commonly observed in patients with low levels of total TILs (p < 0.001), high levels of FOXP3+ TILs (p < 0.001) and low levels of CD8+ TILs (p < 0.001). This served as an independent prognostic factor for both relapse-free survival (Hazard ratio = 1.824, p = 0.013) and overall survival (OS) (Hazard ratio = 2.585, p = 0.001). High expression of PD-L1 was correlated to worse survival, which is most significantly observed in triple-negative patients. Patients classified as PD-L1-high/CD8-low exhibited relatively unfavorable survival, whereas patients with either low expression of PD-L1 or high expression of CD8 had similar outcomes. PD-L1 expression in residual tumor can be used as a prognostic marker in non-pCR patients after receiving NCT for breast cancer, which highlights the importance of immune evasion in the therapeutic vulnerability of chemoresistant cancer cells as well as the potential of anti-PD-L1 treatments in non-pCR responders.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/biosíntesis , Neoplasias de la Mama/química , Linfocitos T CD8-positivos/patología , Linfocitos Infiltrantes de Tumor , Terapia Neoadyuvante , Proteínas de Neoplasias/biosíntesis , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Terapia Combinada , Femenino , Factores de Transcripción Forkhead/análisis , Humanos , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Linfocitos Infiltrantes de Tumor/química , Mastectomía , Persona de Mediana Edad , Neoplasia Residual , Pronóstico , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/cirugía , Microambiente TumoralRESUMEN
PURPOSE: Neoadjuvant chemotherapy (NCT) plus anti-HER2 agents are the standard of care for locally advanced HER2-positive breast cancer. The aim of this study was to evaluate the prevalence and prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without trastuzumab. METHODS: 549 consecutive HER2-positive patients were included in this study. 379 patients were treated with paclitaxel, carboplatin, and trastuzumab (PCH cohort) and 170 were treated with paclitaxel and carboplatin only (PC cohort). Conversion of biomarkers before and after NCT was evaluated via immunohistochemistry (IHC) test. Cox regression model was used to investigate prognostic markers to relapse-free survival (RFS). RESULTS: 50.9% patients were considered as pCR responder in PCH cohort, whereas only 25.9% of patients experienced pCR in PC cohort (P < 0.001). HER2 loss were more frequently shown in PCH cohort with a proportion of 19.8%, compared to 9.4% in PC cohort (P = 0.009). In PCH cohort, patients with a loss of HER2 expression tended to have a higher risk of relapse compared to patients with maintained HER2 expression (HR = 2.639, 95% CI 1.103-6.311, P = 0.029). However, it did not correlate to patient outcome in the PC cohort (P = 0.296). Loss of HER2 was also correlated to ER conversion in PCH cohort. CONCLUSION: Our study has provided new evidence that anti-HER2 treatment has a significant impact on HER2 loss. Far more importantly, the loss of HER2 amplification could identify non-pCR patients with high risk of disease relapse, which might help in tailoring following systemic treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carboplatino/administración & dosificación , Femenino , Amplificación de Genes , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Terapia Neoadyuvante , Metástasis de la Neoplasia , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Pronóstico , Receptor ErbB-2/genética , Factores de Riesgo , Trastuzumab/administración & dosificación , Resultado del TratamientoRESUMEN
PURPOSE: Aspergillosis of the central nervous system is very rare. However with recent increases in the use of immunosuppressive agents and antibiotics, its incidence is increasing. We evaluated the demographics, clinical manifestations, laboratory findings, diagnosis, underlying conditions, treatment regimens and outcomes of patients with cerebral aspergillosis (CA). METHODS: We retrospectively reviewed data from eight patients with CA hospitalized at a Chinese general hospital from 1 January 2005 to 30 September 2015. RESULTS: Common clinical manifestations included headache and cranial nerve involvement. Four patients underwent biopsy and were pathologically diagnosed with Aspergillus hyphae. One patient was proved to have Aspergillus infection via autopsy. One patient had positive cerebrospinal fluid fungal cultures. The lesion locations were: the cavernous sinus (n = 5, 62.5%), frontal lobe (n = 1, 12.5%), temporosphenoid lobe (n = 1, 12.5%) and cerebellum (n = 1, 12.5%). At the end of follow-up, three patients were cured and five patients had died (mortality rate, 62.5%). CONCLUSIONS: Most patients with CA had no significant immunosuppression-related conditions in our study. Aspergillus spp. can infect the central nervous system through several pathways and CA has an atypical clinical manifestation. The use of local tissue puncture, surgery or other invasive means to obtain diseased tissue containing higher levels of Aspergillus, followed by culture or histological examination, can contribute to an early diagnosis of CA and timely therapeutic intervention. The prognosis of CA is poor, but early and adequate use of antifungal drugs with high transfer across the blood-brain barrier and radical surgery to remove lesions can improve the survival rate.
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Aspergilosis/complicaciones , Aspergilosis/patología , Aspergilosis/terapia , Corteza Cerebral/patología , Adulto , Antifúngicos/uso terapéutico , Aspergilosis/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Township and Village Health Services Integration Management (TVHSIM) is an essential form of China's two-tiered health service integration plan at the township and village level.Its main purpose,also one of the target goals in China's new healthcare reform,is to gradually integrate rural health services and appropriately allocate rural health resources.This study aims to assess the village doctors' satisfaction with the TVHSIM and provide scientific base to further improve TVHSIM.A cross-sectional study was carried out in which 162 village doctors from Qinghai,Inner Mongolia and Xinjiang in western China were interviewed.Descriptive analysis,independent t-test,one-way ANOVA,Spearman rank correlation and multiple linear regression were used to analyze the difference and relevance between village doctors' personal characteristics and their satisfaction with TVHSIM and six subscales.Village doctors with different years of practice,social insurance status and essential medical knowledge level showed statistically significant differences in their satisfaction levels (all P<0.05).Age (P<0.05) and years of practice (P<0.01) were negatively correlated with Drug and Medical Device Management and Financing Management.Essential medical knowledge level (P<0.05) was negatively correlated with Operations Management as well.However,social insurance status (P<0.05) was positively correlated with Human Resources Management and Drug and Medical Device management.Gender,age and years of practice respectively had significant influence on village doctors' satisfaction with TVHSIM (P<0.01).In conclusion,in order to further promote TVHSIM policy in rural China,a well-rounded social insurance model for village doctors is urgently needed.In addition,the development of TVHSIM is regionally imbalanced.Efficient and effective measures aiming at rationalizing gender and age structure and enhancing essential medical training should be carefully considered.
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Mitochondrial ribosomal proteins are important for mitochondrial-encoded protein synthesis and mitochondrial function. In addition to their roles in mitoribosome assembly, several mitochondrial ribosome proteins are also implicated in cellular processes like cell cycle regulation, apoptosis, and mitochondrial homeostasis regulation. Here, we demonstrate that MRPL10 regulates cyclin B1/Cdk1 (cyclin-dependent kinase 1) activity and mitochondrial protein synthesis in mammalian cells. In Drosophila, inactivation of mRpL10 (the Drosophila ortholog of mammalian MRPL10) in eyes results in abnormal eye development. Furthermore, expression of human cyclin B1 suppresses eye phenotypes and mitochondrial abnormality of mRpL10 knockdown Drosophila. This study identified that the physiological regulatory pathway of MRPL10 and providing new insights into the role of MRPL10 in growth control and mitochondrial function.
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Ciclina B1/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Ribosómicas/metabolismo , Apoptosis/fisiología , Proteína Quinasa CDC2 , Células Cultivadas , Humanos , Fosforilación , Proteína Ribosómica L10RESUMEN
Neoadjuvant chemotherapy (NCT) is one of the main treatment strategies for patients with locally advanced breast cancer. In this study, we focused on the predictive and prognostic value of Ki-67 in triple-negative breast cancer (TNBC) patients who received NCT. Data from 280 patients with stage II-III TNBC were collected. All patients were treated according to the same protocol with weekly paclitaxel and carboplatin. The overall pCR rate was 33.9%. Both the categorical and linear Ki-67 were independently correlated with pCR (P < 0.001). There were also statistically significant differences among Ki-67 categories with respect to clinical response (P < 0.001), Miller-Payne (MP) grades (P < 0.001), and node status (P < 0.001). A significant reduction of Ki-67 after NCT was most likely observed in patients with a relatively better response. In the multivariate model for non-pCR patients, Ki-67 reduction presented an independent prognostic value for relapse of disease (HR = 0.986, 95% CI: 0.978-0.994; P = 0.001). This study had indicated that the primary Ki-67 might help in further classifying TNBCs into subtypes with different responses to chemotherapy and a significant reduction of Ki-67 after treatment could indicate a favorable prognosis in non-pCR patients.
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Biomarcadores de Tumor/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Adulto , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Paclitaxel/uso terapéuticoRESUMEN
Autoimmune encephalitis associated with anti-voltage-gated potassium channel antibodies are most likely to be misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Our goal was to delineate patients who were initially suspected to have CJD but were later found to have AE. We performed a retrospective clinical review of cases of individuals and made a comparison between groups of patients diagnosed with sCJD and AE. Patients who had rapidly progressing dementia and focal neurological impairment, such as aphasia, gait disturbance, visual disturbance, and depression, at onset were diagnosed with sCJD, whereas epilepsy, hyponatremia and dysautonomia were strong hints for AE. Fluoroscope-positron emission tomography (PET) of patients with AE revealed variable metabolism and normative and long-term immunosuppression were less likely to relapse.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/fisiopatología , Poliendocrinopatías Autoinmunes/diagnóstico , Anciano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/inmunología , Diagnóstico Diferencial , Electroencefalografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas del Tejido Nervioso/inmunología , Proteínas del Tejido Nervioso/metabolismo , Poliendocrinopatías Autoinmunes/fisiopatología , Tomografía de Emisión de Positrones , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
To explore the novel application of boron nitride nanotubes (BNNTs), we investigated the interaction of pentachlorophenol (PCP) pollutant with the pristine and Fe doped (Fe-doped) (8, 0) single-walled BNNTs by performing density functional theory calculations. Compared with the weak physisorption on the pristine BNNT, PCP molecule presents strong chemisorption on the Fe-doped BNNT. The calculated data for the electronic properties indicate that doping Fe atom into the BNNT significantly improves the electronic transport property of BNNT, induces magnetism in the BNNT, and increases its adsorption sensitivity toward PCP molecule. It is suggested that doping BNNTs with Fe is an available strategy for improving the properties of BNNTs, and that Fe-doped BNNT would be a potential resource for adsorbing PCP pollutant in environments.