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Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
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Xantomatosis Cerebrotendinosa , Humanos , Masculino , Adulto , Femenino , Xantomatosis Cerebrotendinosa/genética , Xantomatosis Cerebrotendinosa/diagnóstico , Xantomatosis Cerebrotendinosa/patología , Linaje , Colestanotriol 26-Monooxigenasa/genética , Mutación , AtaxiaRESUMEN
Objective: To analyze the disease burden of pancreatic cancer in major Asian countries and forecast the burden of that in China, which helps to provide reference for the prevention and control of pancreatic cancer. Methods: Data on disease burden of pancreatic cancer among global and major Asian countries from on the Global Burden of Disease (GBD) 2019 were collected to describe burden distribution through the absolute numbers or standardized rates of incidence, death and disability adjusted life years (DALY) by year, sex and socio-demographic index. Estimated annual percentage changes (EAPC) was used to assess the trend of standardized rate. The proportion of deaths attributable to risk factors for pancreatic cancer in 2019 was used to compare by age, sex and region. ARIMA model was performed with R language to predict change of age-standardized incidence and death rates of pancreatic cancer from 2020 to 2029. Results: From 1990 to 2019, the standardized incidence rates of pancreatic cancer in China increased from 3.17/100 000 to 5.78/100 000, and the standardized death rate increased from 3.34/100 000 to 5.99/100 000. The increases exceeded other high-income Asia countries. In the past three decades, the standardized incidence, death and DALY rates of pancreatic cancer in global have increased year by year. Among the major countries in Asia, China has the highest growth rate of disease burden (EAPC of standardized incidence rates=2.32%, 95% CI: 2.10%-2.48% and EAPC of standardized death rate=2.25%, 95% CI: 2.03%-2.42%). In addition, incidence and death rates of pancreatic cancer in China are expected to continue on the rise between 2000 and 2029 by ARIMA model. Incidence rate is expected to increase 15.92% and death rate is expected to increase 15.86%. Conclusions: The standardized incidence and death rates of pancreatic cancer in China increase year by year with an increasing trend for the burden of disease. The disease burden of pancreatic cancer is expected to rise due to the increase and aging of the population. Preventive measures should be adopted to decrease the burden of the pancreatic cancer.
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Carga Global de Enfermedades , Neoplasias Pancreáticas , Asia/epidemiología , Humanos , Incidencia , Neoplasias Pancreáticas/epidemiología , Factores de Riesgo , Neoplasias PancreáticasRESUMEN
Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.
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Neoplasias de la Mama , Mama , Femenino , Humanos , Persona de Mediana Edad , Adolescente , Adulto Joven , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Estudios Retrospectivos , Estudios de Casos y Controles , Mama/patología , Neoplasias de la Mama/patologíaRESUMEN
Objective: To investigate the clinical value of neutrophil-lymphocyte ratio (NLR), fibrinogen (FIB), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in the diagnosis and prognosis of colorectal cancer. Methods: A case-control study design was used to select 155 patients with colorectal cancer[98 males and 57 females, aged (63.12±13.99)years old], 90 patients with colorectal polyps[62 males and 28 females, aged (56.86±12.74)years old] and 150 healthy subjects[93 males and 57 females, aged (57.02±10.91)years old] from the First Affiliated Hospital of Nanjing Medical University from October 2017 to March 2018. Blood routine tests were detected by instrument method, FIB was detected by Clauss method, and CEA and CA19-9 were detected by electrochemiluminescence method. The levels of the NLR, FIB, CEA and CA19-9 in the 3 groups were compared. The diagnostic efficacy of NLR, FIB, CEA and CA19-9 of colorectal cancer was compared according to the ROC curve. The relationship between the level of NLR, FIB, CEA and CA19-9 and their clinicopathological features in colorectal cancer patients was assessed. According to the median levels of NLR, FIB, CEA and CA19-9, 112 follow-up of colorectal cancer patients could be divided into the high-value group and the low-value group. Kaplan-Meier, log-rank test and Cox regression analysis were used to analyze the relationship between the levels of the four indicators and the prognosis of colorectal cancer. Results: The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were 2.11(1.52, 2.86), 3.21(2.58, 3.86)g/L, 3.93(2.27, 8.78)µg/L, 15.11(9.10, 25.73)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were 1.74(1.39, 2.17), 2.54(2.26, 3.03)g/L, 1.99(1.18, 2.70)µg/L, 9.83(6.13, 15.68)U/ml. The levels of NLR, FIB, CEA and CA19-9 in healthy control group were 1.68(1.33, 2.28), 2.56(2.30, 2.82)g/L, 1.85(1.28, 2.59)µg/L, 10.03(6.86, 13.26)U/ml. The levels of NLR, FIB, CEA and CA19-9 in colorectal cancer group were significantly higher than those in colorectal polyp group (Z values were 3.568, 5.913, 6.880 and 4.022,P values were all<0.05) and healthy control group(Z values were 3.916, 7.381, 9.131 and 5.251,P values were all<0.05). The levels of NLR, FIB, CEA and CA19-9 in colorectal polyp group were not remarkably different from those in healthy control group (Z values were 0.217, 0.179, 0.320 and 0.061,P values were all>0.05). The diagnostic performance of CEA was the best in single test, followed by FIB, CA19-9 and NLR. The sensitivity of combined NLR+FIB+CEA or NLR+FIB+CEA+CA19-9 was the highest with 72.3%. NLR and FIB levels were associated with tumor sites (Z values were 3.587 and 7.089,P values were both<0.05). FIB and CEA levels were correlated with the depth of tumor invasion (Z values were 3.250 and 3.245, P values were both <0.05). NLR, FIB, CEA and CA19-9 levels were both associated with lymph node metastasis (Z values were 2.010, 3.276, 3.312 and 2.921, P values were all<0.05). The prognosis of patients in the high-value NLR, FIB, CEA and CA19-9 groups was significantly worse than that in the low-value group (χ2 values were 5.744, 6.048, 4.389 and 6.942,P values were all<0.05).Cox multivariate regression analysis showed lymph node metastasis, NLR >2.15 and CA19-9 >15.47 U/ml are independent factors affecting the prognosis of colorectal cancer. Conclusion: NLR, FIB, CEA and CA19-9 can be applied in the auxiliary diagnosis and prognosis of colorectal cancer.
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Antígeno CA-19-9 , Neoplasias Colorrectales , Adulto , Anciano , Biomarcadores de Tumor , Antígeno Carcinoembrionario , Estudios de Casos y Controles , Neoplasias Colorrectales/diagnóstico , Femenino , Fibrinógeno , Humanos , Linfocitos , Masculino , Persona de Mediana Edad , NeutrófilosRESUMEN
To investigate the risk factors of lymph node metastasis in early gastric cancer (EGC) and to develop a risk model for the presence of lymph node metastasis. A total of 172 EGC patients, with a median age of 62(52, 68) years, who underwent gastric cancer resection in the First Affiliated Hospital of Nanjing Medical University from January 2017 to June 2019 were selected. Clinical data of the patients were collected through the case system. Logistic regression analysis was used to determine the variables significantly related to lymph node metastasis. ROC curve and calibration curve were used to evaluate the risk model. The results showed that the lymph node metastasis rate of 172 EGC patients was 19.19% (33/172). Tumor size, depth of invasion, degree of differentiation and vascular tumor thrombus were associated with lymph node metastasis (P<0.05), but age ≥ 60 years (OR=5.556, 95%CI: 1.757-17.569, P=0.004), invasion depth (OR=4.218,95%CI:1.418-12.548, P=0.010) and vascular cancer embolus (OR=13.878,95%CI:4.081-47.196,P<0.001) were independent risk factors for lymph node metastasis of EGC. The consistency index of the risk model based on the above risk factors was 0.8835 (95%CI: 0.818 8-0.948 2). The calibration curve shows that the risk assessment model is in good agreement with the actual results, indicating that the model has high accuracy and discrimination.The most common site of metastasis was group 3, followed by group 4. Therefore, patients over 60 years old with submucosal invasion and vascular tumor thrombus may have a higher risk of lymph node metastasis.
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Neoplasias Gástricas , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Objective: To investigate the auxiliary diagnostic value of seven tumor-associated autoantibodies (AABs) P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE in early non-small cell lung cancer (NSCLC). Methods: The case-control study enrolled 195 patients with early NSCLC [71 males and 124 females, aged (55.70±11.78) years old], 114 patients with benign lung disease [44 males and 70 females, aged (52.85±12.31) years old] and 100 healthy subjects [39 males and 61 females, aged (53.62±9.97) years old] from the First Affiliate Hospital of Nanjing Medical University from June 2020 to December 2020. AABs were detected by enzyme-linked-immunosorbent serologic assay (ELISA), and carcinoembryonic antigen (CEA),cytokeratin 19-fragments (CYFRA21-1) and neuron specific enolase (NSE) were detected by electrochemiluminescence. The levels of AABs,CEA,CYFRA21-1 and NSE in the 3 groups were compared. Patients with benign lung diseases and healthy subjects were combined into the control group, and the positive rate of each indicator in the NSCLC group and the control group was compared. The diagnostic efficacy of single and combined tests for NSCLC were obtained using receiver operating characteristic (ROC) curves. Besides, the relationship between the levels of AABs, CEA, CYFRA21-1 and NSE and their clinicopathological features and preoperative imaging parameters in NSCLC patients was assessed. Results: The levels of SOX2 [0.70 (0.10, 2.40) U/mL] and GBU4-5 [1.30 (0.30, 8.90) U/mL] in NSCLC group were higher than those in benign disease group [SOX2: 0.50 (0.10, 1.60) U/mL, GBU4-5: 0.80 (0.10, 2.30) U/mL, Z values were 27.258 and 45.797; P values were all<0.05] and health control group [SOX2: 0.45 (0.10, 1.08) U/mL, GBU4-5: 0.75 (0.20, 1.78) U/mL, Z values were 32.551 and 40.456; P values were all<0.05], and there was no significant difference between benign disease group and health control group (Z values were 5.293 and 5.340, P values were all>0.05). The levels of CEA [1.75 (1.08, 2.72) U/mL] and CYFRA21-1 [1.81 (1.41, 2.36) U/mL] in NSCLC group were higher than those in healthy control group [CEA: 1.22 (0.68, 1.81) U/mL, CYFRA21-1: 1.43 (1.14, 1.74) U/mL, Z values were 64.100 and 37.597; P values were all<0.05], but there was no significant difference between NSCLC group and benign group [CEA: 1.74 (1.01, 2.51) U/mL, CYFRA21-1: 1.82 (1.45, 2.46) U/mL, Z values were 7.275 and 10.621; P values were all>0.05]. The positive rates of P53, SOX2, GAGE7, GBU4-5 and CEA in NSCLC group were higher than those in the control group [P53: 10.3% vs 0.9%, SOX2: 11.3% vs 2.3%, GAGE7: 11.3% vs 0.5%, GBU4-5: 30.1% vs 5.6%, CEA: 9.7% vs 0.9%, χ2 values were 17.420, 13.242, 22.485, 43.211, 16.255, respectively; P values were all<0.05]. The diagnostic efficiency of the combined detection of seven AABs was better than that of single detection. Seven AABs combined with CEA [area under curve (AUC): 0.732, sensitivity: 64.10%] and with CYFRA21-1 (AUC: 0.737, sensitivity: 58.97%) greatly improved the diagnostic efficiency and sensitivity of CEA (AUC: 0.583, sensitivity: 50.77%) and CYFRA21-1 (AUC: 0.552, sensitivity: 44.10%). The levels of SOX2 and CEA in NSCLC patients were correlated with the degree of tumor invasion (H values were 6.436 and 14.071; P values were all<0.05); the levels of GAGE7 and CEA were correlated with the nodule density (H values were 7.643 and 12.268; P values were all<0.05); and the levels of SOX2, GAGE7, CEA and CYFRA21-1 were all correlated with the nodule size (H values were 10.837, 11.528, 31.835, 20.338; P values were all<0.05). Conclusion: The detection of AABs combined with CEA and CYFRA21-1 is helpful for the early auxiliary diagnosis of NSCLC, and plays an important role in prevention and screening for early lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Anciano , Antígenos de Neoplasias , Autoanticuerpos , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Estudios de Casos y Controles , Femenino , Humanos , Queratina-19 , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To search age-correlated facial features and construct an age estimation model based on the three-dimensional ï¼3Dï¼ facial images of Xinjiang Uygur males, and to structure individual face images of old age and young age. METHODS: Pretreatment was performed to collect 105 3D facial images of Xingjiang Uygur males aged between 17-57 years by Artec Studio software. The facial images were transferred to high-density 3D dot matrix data by FaceAnalysis software, and each image could be represented with 32 251 vertexes. Central correction of the facial images was done and all the data were aligned to a standard coordinate frame by generalized Procrustes analysis ï¼GPAï¼. The age estimation model was established by partial least square regression ï¼PLSRï¼. Furthermore, the changes of age-correlated facial features were presented on the heat map of average face, and the reconstruction of facial images at different ages was performed based on this model. RESULTS: With age, the average faces showed a series of changes including the nasolabial sulcus deepening, cheek sinking, cheekbone protruding and eye corner drooping. The Pearson correlation coefficient ï¼rï¼ between estimated age and chronological age was 0.71. The mean absolute deviation ï¼MADï¼ of age estimation was 6.37 years. The results of age estimation in >30-40 years group showed a best accuracy ï¼MAD=4.27 yearsï¼, and the deviations increased with age after 40 years. The composite facial images represented a significant result with age on facial morphological features and aging. CONCLUSIONS: The results of this study reveal the age-correlated facial features and aging markers in Uygur population, which help to construct a reliable age estimation model.
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Envejecimiento/fisiología , Cara/anatomía & histología , Cabeza/anatomía & histología , Imagenología Tridimensional/métodos , Adolescente , Adulto , Humanos , Masculino , Persona de Mediana Edad , Programas Informáticos , Adulto JovenRESUMEN
In this study, we investigated the role of ADH2 Arg47His and ALDH2 Glu487Lys genetic polymorphisms in the development of Parkinson's disease in a Chinese population. Between January 2013 and May 2014, 115 patients with Parkinson's disease and 214 healthy controls were recruited in our study. Genotyping of ADH2 Arg47His and ALDH2 Glu487Lys polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism method. In the dominant model, the GA + AA genotype of ALDH2 Glu487Lys was found to be significantly associated with elevated risk of Parkinson's disease when compared with the GG genotype [odds ratio = 1.71, 95% confidence interval (CI) = 1.02-2.84]. In the recessive model, the AA genotype of ALDH2 Glu487Lys showed a 4.87-fold increase (95%CI = 1.54-18.03) in the risk of Parkinson's disease when compared to the GG and GA genotypes. However, no significant association was found between the ADH2 Arg47His polymorphism and risk of Parkinson's disease in the co-dominant, dominant, or recessive models. In conclusion, our study suggests that the ALDH2 polymorphism could influence the development of Parkinson's disease in the Chinese population studied here.
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Alcohol Deshidrogenasa/genética , Aldehído Deshidrogenasa Mitocondrial/genética , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Expresión Génica , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Oportunidad Relativa , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/etnología , Enfermedad de Parkinson/patología , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
The aim of the current study was to examine the protective effects and mechanisms of Ndfipl on neurocytes in an experimental in vitro Parkinson's disease model induced by MPP+. The cell model was developed with dominant negative expression and suppressed expression of Ndfipl by means of transient transfection of Ndfipl-dominant negative and -inhibitory vectors. In total, four different Ndfipl cell models were established. Different methods were used to analyze the cells. The MTT method was used to detect the effect of Ndfipl on the survival rate and apoptosis of the cells induced by MPP(+). We further studied the roles of Ndfipl in inhibiting MPP(+)-induced SH-SY5Y apoptosis, protection, and ubiquitination of SH-SY5Y cells. Our results showed that Ndfipl reduced apoptosis and improved cell survival rate, indicating that Ndfipl has a neuroprotective effect. Furthermore, we found that Ndfipl binds to Nedd4-1, and that increased expression of Ndfipl significantly reduced Itch expression. We also found that increased ubiquitination played a role in Ndfipl-mediated processes, and that Ndfipl and α-synuclein interact. Additionally, the expression of Ndfipl reduced expression of α-synuclein. In conclusion, Ndfipl plays a significant role in protecting SH-SY5Y cells in in vitro Parkinson's disease models.
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Apoptosis/genética , Proteínas Portadoras/biosíntesis , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Proteínas de la Membrana/biosíntesis , Enfermedad de Parkinson Secundaria/genética , Ubiquitina-Proteína Ligasas/genética , alfa-Sinucleína/biosíntesis , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/efectos adversos , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Intoxicación por MPTP , Ubiquitina-Proteína Ligasas Nedd4 , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/patología , Especies Reactivas de Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , alfa-Sinucleína/genéticaRESUMEN
We investigated the effects of hyperbaric oxygen treatment on the Nrf2 signaling pathway in secondary injury following traumatic brain injury, using a rat model. An improved Feeney freefall method was used to establish the rat traumatic brain injury model. Sixty rats were randomly divided into three groups: a sham surgery group, a traumatic brain injury group, and a group receiving hyperbaric oxygen treatment after traumatic brain injury. Neurological function scores were assessed at 12 and 24 h after injury. The expression levels of Nrf2, heme oxygenase 1 (HO-1), and quinine oxidoreductase 1 (NQO-1) in the cortex surrounding the brain lesion were detected by western blotting 24 h after the injury. Additionally, the TUNEL method was used to detect apoptosis of nerve cells 24 h after traumatic injury and Nissl staining was used to detect the number of whole neurons. Hyperbaric oxygen treatment significantly increased the expression of nuclear Nrf2 protein (P < 0.05), HO-1, and NQO-1 in the brain tissues surrounding the lesion after a traumatic brain injury (P < 0.05) and also significantly reduced the number of apoptotic and injured nerve cells. The neurological function scores also improved with hyperbaric oxygen treatment (P < 0.05). Therefore, hyperbaric oxygen has a neuroprotective role in traumatic brain injury, which is mediated by up-regulation of the Nrf2 signaling pathway.
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Lesiones Traumáticas del Encéfalo , Corteza Cerebral , Oxigenoterapia Hiperbárica , Factor 2 Relacionado con NF-E2 , Transducción de Señal , Regulación hacia Arriba , Animales , Masculino , Ratas , Apoptosis , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/terapia , Corteza Cerebral/metabolismo , Corteza Cerebral/fisiopatología , Modelos Animales de Enfermedad , Hemo Oxigenasa (Desciclizante)/genética , NAD(P)H Deshidrogenasa (Quinona)/genética , Neuronas/metabolismo , Neuronas/fisiología , Factor 2 Relacionado con NF-E2/genéticaRESUMEN
It is expensive to induce experimental autoimmune myasthenia gravis (EAMG) by active immunity, and difficult to obtain natural acetylcholine receptor (AChR). We sought a new method of inducing EAMG by immunizing rats with artificially synthesized AChR. The AChR mRNA in TE671 cells was extracted and reverse transcribed. The inclusion body was purified and protein concentration was determined, and the EAMG animal model was used for induction. The serum was extracted from rat blood. The antibody titer was determined using enzyme-linked immunosorbant assay (ELISA). The concentration of decay accelerating factor (DAF) in the rat serum was determined by ELISA, and the metabolism of serum rDAF was determined by western blot. We evaluated the inhibition of rDAF by determining the 50% complement hemolysis unit in the rat serum. The extracellular domain (ECD) nucleotide sequence clone produced by polymerase chain reaction was completely consistent with that in the human gene bank; it was induced by isopropyl ß-D-1-thiogalactopyranoside to express the protein after insertion into vector pET16b. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the inclusion body protein was the exact target. The ECD protein was able to bind with mAb35 after dialysis and renaturation, which demonstrated protein activity. The soluble ECD protein was used to immunize rats and obtain the EAMG models. The inhibitory effect of the complement was unsatisfactory owing to high decay rate after rDAF injection into the EAMG models. It is easy to induce the EAMG model by obtaining the AChRTEα1 subunit ECD protein using the substitution method.
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Antígenos CD55/uso terapéutico , Miastenia Gravis Autoinmune Experimental/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Animales , Antígenos CD55/administración & dosificación , Antígenos CD55/sangre , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inyecciones Intravenosas , Miastenia Gravis Autoinmune Experimental/sangre , Miastenia Gravis Autoinmune Experimental/patología , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/farmacología , Renaturación de Proteína/efectos de los fármacos , Estructura Terciaria de Proteína , Ratas Endogámicas Lew , Proteínas Recombinantes/metabolismo , SolubilidadRESUMEN
We investigated protein expression in the medullary visceral zone (MVZ) of rats with multiple-organ dysfunction syndrome (MODS) caused by subarachnoid hemorrhage (SAH) to discuss the possible regulatory mechanism of the MVZ in the course of SAH-induced MODS. A SAH-induced MODS model was established in rats by injecting arterial blood into the Willis' circle. Protein expression in the MVZ was analyzed by immunohistochemistry assay. Protein expression in the MVZ peaked 24-36 h after SAH, and was significantly higher than in the control and sham operation groups. Organs at each time point exhibited inflammatory injuries to varying degrees after SAH, which reached a maximum at 24-36 h. Incidences of systemic inflammatory response syndrome and MODS were 100 and 71.67%, respectively, after SAH. There is a consistency between MVZ protein expression and inflammatory changes in each organ after SAH. This prompts the suggestion that the MVZ may be one of the direct regulative centers in SAH-induced MODS, and may be involved in the functional regulation of the surrounding organs after SAH.
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Bulbo Raquídeo/metabolismo , Hemorragia Subaracnoidea/metabolismo , Animales , Lesiones Encefálicas/metabolismo , Estudios de Casos y Controles , Círculo Arterial Cerebral/metabolismo , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/metabolismo , Ratas , Ratas Wistar , Hemorragia Subaracnoidea/sangreAsunto(s)
Antineoplásicos/uso terapéutico , Terapia Molecular Dirigida/tendencias , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Gástricas/terapia , Antineoplásicos/efectos adversos , Humanos , Terapia Molecular Dirigida/métodos , Neoplasias Gástricas/patología , Neoplasias Gástricas/fisiopatologíaRESUMEN
Objective: To explore high-risk sexual behaviors of HIV/AIDS and related factors in young students in Guangzhou. Methods: A cross-sectional survey was conducted in 5 different types of Guangzhou colleges by convenience sampling with minimum number of classes per grade and 600 samples per school from September to November 2021. The R 4.2.2 software was used to consolidate databases. Simultaneously, a logistic regression model and a decision tree algorithm model, stratifying by whether sexual behaviors had occurred before, were constructed. In each layer, the prediction performance of the two models was evaluated through area under receiver operating characteristic and the confusion matrix, and then the model with high prediction performance was retained. Results: A total of 7 346 students were surveyed. The proportion of the respondents reporting sexual experience were 9.08% (667/7 346), in whom 26.24% (175/667) had risky sexual activity in the past year. The decision tree algorithm model performs well in predicting whether high-risk sexual behaviors have occurred in the past year. When the complexity parameter value is 0.018, and nsplit reaches 4, which means there are 5 leaf nodes in the model, the cross error of the tree will be the smallest. The first best grouping variable in the decision tree was whether to use condoms throughout the first sexual behavior. If condoms were used at their sexual debut, but homosexual practices have occurred in the past year, the probability of risky sexual behavior will increase. If homosexual practices have not occurred in the past year, but the age of sexual debut was below 18 years old while the period of HIV education was after high school, the probability of risk sexual behavior will also increase. Conclusions: AIDS-related risky behaviors of young students still deserved attention. The experience of sexual debut and whether AIDS-related health education has been received before the sexual debut were significant predictors for the occurrence of high-risk sexual behavior. The decision tree algorithm model has particular applicability for predicting and screening potential risk populations.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Adolescente , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Estudios Transversales , Conducta Sexual , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Condones , Factores de Riesgo , Estudiantes , Asunción de Riesgos , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Objective: To investigate the risk perception for risky behavior of HIV/AIDS infection among young students and to analyze the related influencing factors. Methods: A cross-sectional survey was conducted in 5 different types of Guangzhou colleges from September to November 2021, in which convenience sampling and a minimum number of classes per grade and 600 samples per school were used according to the national unity program. Disordered multi-classification logistic regression was used to construct a risk perception model and analyze influencing factors in different risk perception levels. Results: A total of 7 346 young students were surveyed, and most rated themselves at low risk of HIV/AIDS infections (90.58%, 6 654/7 346). A total of 89.10% (6 545/7 346) of subjects' perception of their HIV/AIDS infection risk was consistent with their risk behavior, while 10.90% (801/7 346) was inconsistent. Among those inconsistent subjects, 19.10% (153/801) showed underestimating their risk , while 80.90% (648/801) seen overestimating their risk. Disordered multi-classification logistic regression analysis showed that, after controlling for other factors, compared with the non-sexual group, respondents whose first sex age under 18 had a higher rate of underestimating their risk of infection (OR=129.39, 95%CI: 73.28-228.48), as well as a higher rate of overestimated their risk of infection (OR=1.76, 95%CI: 1.04-2.99). First sexual intercourse at age 18 or older was a risk factor for underestimating risk (OR=70.56, 95%CI: 42.72-116.53), but was not statistically associated with overestimating risk. Being female, other school type, non-heterosexual orientation, and self-rated HIV-related knowledge as fair or no knowledge were risk factors for overestimating risk but were not statistically associated with underestimating risk. Conclusions: Overall, young students in universities of Guangzhou have a good risk perception of HIV/AIDS infection. Individual factors, education factors and sexual experience will influence students' risk perception of HIV/AIDS infection. Raising the awareness rate of HIV/AIDS knowledge and delaying the age of first sexual intercourse will improve the risk perception ability of young students.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Femenino , Adolescente , Masculino , Estudios Transversales , Infecciones por VIH/epidemiología , Conducta Sexual , Estudiantes , Encuestas y Cuestionarios , Percepción , Conocimientos, Actitudes y Práctica en SaludRESUMEN
BACKGROUND AND PURPOSE: Owing to its low morbidity but high mortality, no accurate scoring system focuses on primary pontine hemorrhage (PPH) has been established. We aim to compare the performances of the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Simplified Acute Physiology Score (SAPS) II with the ICH score in predicting the 30-day mortality in patients with PPH. METHODS: We conducted a retrospective analysis of patients admitted with a diagnosis of PPH to a university-affiliated hospital in southern China from May 2000 to June 2011. Data related to patient demographics and that necessary to calculate APACHE II, SAPS II, and ICH score were recorded. Performances of these scoring systems were presented as calibration and discrimination, which were measured by the Hosmer-Lemeshow goodness-of-fit test and the area under the receiver operating characteristic (ROC) curve, respectively. RESULTS: Among 75 patients with PPH finally included, 31 (41.3%) died within 30 days. SAPS II (χ(2) = 6.57, P = 0.682) had the best calibration, followed by APACHE II (χ(2) = 8.06, P = 0.428) and ICH score (χ(2) = 4.94, P = 0.176). Furthermore, in terms of area under the ROC curve, APACHE II (0.919) was more discriminative than SAPS II (0.890) and ICH score (0.844). CONCLUSIONS: In predicting 30-day mortality in patients with PPH, SAPS II has the best calibration, while APACHE II has the highest discrimination. The ICH score, which is easier and simpler to calculate, should be modified for PPH.
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Hemorragias Intracraneales/mortalidad , Puente/patología , APACHE , Adulto , Anciano , Femenino , Humanos , Hemorragias Intracraneales/clasificación , Hemorragias Intracraneales/diagnóstico , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Tibial dyschondroplasia (TD) is characterized by expansion of the proximal growth plates of the tibiotarsus that fail to form bone, lack blood vessels, and contain non-viable cells. Thiram (a carbamate pesticide), when fed to young broiler chicks, induces TD with high regularity and precision. We used this experimental model to understand the cause of the defects associated with TD by selecting and identifying the genes differentially expressed in the TD growth plate of broiler chickens. Broiler chicks at 7 days of age were randomly divided into two groups. After fasting overnight, they were fed with regular diet (control) or the same diet containing 100 mg/kg thiram for 96 h to induce TD (thiram-fed). mRNA was purified from the growth plates of control and thiram-fed broilers. Forward and reverse-subtracted cDNA libraries were generated by suppression subtractive hybridization technology. Ten selected genes from cDNA libraries were identified by real-time quantitative polymerase chain reaction. All were differentially expressed in TD growth plates (P<0.05 or P<0.01). The levels of collagen type X (Col X), pro-alpha-1 collagen type I (Col I alpha1), collagen type IX (Col IX), NADH dehydrogenase (NADH DH), cytochrome C oxidase subunit III (COX III), enolase 1, alpha (ENO1), carbonic anhydrase II (CA2) and heat shock protein 90 (Hsp90) mRNA transcripts were up-regulated, while the expression levels of Matrilin 3 (MATN3) and chondromodulin-I (ChM-I) were down-regulated. Col I and Hsp90 were detected by immunohistochemistry at different stages. Given that these genes are involved in matrix formation, endochondral ossification, developmental regulation, electron transport in the mitochondrial respiratory chain and vascularization, our findings may provide new insights into understanding the pathogenesis of TD.
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Regulación de la Expresión Génica , Placa de Crecimiento/patología , Osteocondrodisplasias/inducido químicamente , Osteocondrodisplasias/veterinaria , Enfermedades de las Aves de Corral/inducido químicamente , Enfermedades de las Aves de Corral/genética , Tiram/toxicidad , Tibia/patología , Alimentación Animal/toxicidad , Animales , Pollos , Cartilla de ADN , ADN Complementario/genética , Fungicidas Industriales/toxicidad , Biblioteca de Genes , Placa de Crecimiento/efectos de los fármacos , Inmunohistoquímica , Osteocondrodisplasias/genética , Osteocondrodisplasias/patología , Reacción en Cadena de la Polimerasa , Enfermedades de las Aves de Corral/patología , ARN Mensajero/genéticaRESUMEN
Bis(7)-tacrine was evaluated for efficacy on memory retention in mice 17 days of age and 30 days of age. The tests used were a passive-avoidance response test and a measure of spontaneous motor activity. Also, possible drug-induced hepatotoxicity and acute drug toxicity were evaluated. Behavioral studies were performed using a step-through task and an open-field test with a 24-h interval between training and evaluation tests. Bis(7)-tacrine (0.06-20 micromol/kg) was subcutaneously injected 30 min prior to the first session of both test types. During the training session of the step-through task, bis(7)-tacrine treatment reduced (by 46%, P<0.01) the number of avoidable electric shocks (footshocks) only at a high dose of 20 micromol/kg in mice 17 days of age, but dose-dependently decreased the number of footshocks (10-56%, P<0.001) in mice 30 days of age. Bis(7)-tacrine treatment at all doses tested did not produce any detectable changes in retention latency in mice 17 days of age, but the drug significantly prolonged retention latency at low doses (1.25 and 2.50 micromol/kg), and not high doses (5-20 micromol/kg), in mice 30 days of age. In the open-field test, bis(7)-tacrine decreased spontaneous motor activity in the acquisition session only at a high dose of 20 micromol/kg in mice 17 days of age and 30 days of age (by 28 and 45%, respectively), but did not affect spontaneous motor activity in the recall session. Bis(7)-tacrine treatment at a dose of 20 micromol/kg produced a more potent hepatotoxic effect in mice 30 days of age than in mice 17 days of age, (P<0.05), and the drug caused acute toxicity with comparable potencies in mice of both age groups. In conclusion, mice 30 days of age seemed to be more sensitive than mice 17 days of age to bis(7)-tacrine-induced cognitive function enhancement and hepatotoxicity. Bis(7)-tacrine appears to be more potent and more selective as a cognitive function-enhancing agent than tacrine.
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Conducta Animal/efectos de los fármacos , Tacrina/análogos & derivados , Factores de Edad , Animales , Reacción de Prevención/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Actividad Motora/efectos de los fármacos , Nootrópicos/administración & dosificación , Nootrópicos/farmacología , Nootrópicos/toxicidad , Tacrina/administración & dosificación , Tacrina/farmacología , Tacrina/toxicidadRESUMEN
The potential of tacrine in altering cognitive/behavioral function as well as in causing toxicity was evaluated in mice of 17 and 30 days of age. Cognitive and behavioral studies were performed using a step-through passive avoidance task and a habituation open-field test with a 24-h retention interval. Tacrine was subcutaneously injected (1.25-80 micro mol/kg) 30 min prior to the first session of both tests. During the training session in step-through task, tacrine treatment dose-dependently decreased the number of footshocks, with IC(50) values being 7.8 and 23.3 micro mol/kg in 17- and 30-day-old mice, respectively. Treatment with tacrine at a low dose (5 micro mol/kg) significantly prolonged the retention latency in 17-day-old mice only, but it shortened the retention latency at high doses of 20 and 40 micro mol/kg in 17- and 30-day-old, respectively. During the acquisition session in the open-field test, tacrine treatment dose-dependently decreased the locomotor activity in 17- and 30-day-old mice, with IC(50) values being 15.1 and 24.7 micro mol/kg, respectively. High doses of tacrine invariably increased the locomotor activity during the recall session. Tacrine treatment at a dose of 40 micro mol/kg caused a significant increase in serum alanine aminotransferase activity in 17- and 30-day-old mice at 6 h post-dosing, with the extent of stimulation in 30-day-old mice being more prominent. In conclusion, tacrine was more potent in enhancing/disrupting the cognitive function, inhibiting locomotor activity as well as in causing hepatotoxicity in 17-day-old than in 30-day-old mice.
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Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Tacrina/toxicidad , Animales , Defecación/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hígado/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICRRESUMEN
OBJECTIVE: Potential additive effects of estrogens and sevoflurane against cerebral infarction after transient or permanent middle cerebral artery occlusion (MCAO) have not been addressed. We evaluated these using a rat model of MCAO. MATERIALS AND METHODS: 60 adult female Sprague-Dawley rats were used in the experiments after ovariectomy. Animals were divided into placebo/no MCAO, placebo + MCAO, and estrogen + MCAO groups. Each group was further subdivided into subgroups exposed to sevoflurane or oxygen. Animals in the placebo group received intraperitoneal injections of saline, whereas the estrogen group animals received intraperitoneal injections of estradiol (1 mg per day). MCAO was performed 1 week after the ovariectomy. Sevoflurane and oxygen subgroups breathed either sevoflurane or oxygen for 30 min during the surgery. Outcomes were the levels of serum estradiol (E2), interleukin (IL)-6, and beta-amyloid protein (ß-AP) (all by ELISA), neurological deficit scores (24 hours, 7 and 28 days after the operation), spatial learning and memory (both by the Morris water maze test on days 7 and 28). RESULTS: MCAO significantly up-regulated serum levels of IL-6 and ß-AP (p < 0.05 for both comparisons). The animals that received the combined treatment with estrogen and sevoflurane showed less extensive up-regulation of these markers (p < 0.05 vs. placebo-treated animals). Furthermore, MCAO induced severe neurological dysfunction and disorders of spatial learning and memory. All these were attenuated by the combined treatment. CONCLUSIONS: We demonstrate neuroprotective effects of pre-conditioning with estrogen and post-conditioning sevoflurane in experimental animal undergoing MCAO.