Relação entre Níveis Plasmáticos Aumentados de Legumain e Propriedades da Placa Aterosclerótica Coronária / Relationship between Increased Plasma Levels of Legumain and Properties of Coronary Atherosclerotic Plaque

Resumo Fundamento Muitos estudos clínicos confirmaram que a legumain está intimamente relacionada à aterosclerose. Infelizmente, chegaram-se a conclusões diferentes e ainda faltam análises e estudos sobre as características da placa aterosclerótica em pacientes com níveis plasmáticos aumentados de legumain. Objetivos Este estudo teve como objetivo investigar a correlação entre as características da legumain e da placa aterosclerótica coronariana. Métodos Um total de 81 pacientes com doença cardíaca aterosclerótica coronariana (DCAC), incluindo 43 pacientes com angina instável (AI) e 38 pacientes com angina estável (AE), foram examinados por angiografia coronária. Foi realizado ultrassom intravascular (IVUS) para avaliar as características das placas ateroscleróticas coronarianas, e os níveis plasmáticos de legumain também foram medidos. Valores de p < 0,05 foram considerados significativos. Resultados A concentração de legumain foi significativamente maior nos dois subgrupos de doença coronariana do que no grupo controle (todos p<0,001). As concentrações de legumain no grupo AI foram significativamente maiores do que no grupo SA (p=0,001). A área de placa, o índice de remodelamento (IR) e o índice de excentricidade (IE) no grupo AI foram significativamente maiores do que no grupo AE (p<0,001, p=0,001, p=0,001, respectivamente). Houve uma correlação positiva significativa entre os níveis de legumain e IR e IE em pacientes com AI e AE (todos p<0,05). Conclusões Níveis plasmáticos elevados de legumain estavam intimamente relacionados com a ocorrência e gravidade da doença coronariana, e as lesões tendiam a ser instáveis. Espera-se que a legumain seja um potencial biomarcador inflamatório para o diagnóstico de doença coronariana e a identificação precoce de lesões coronárias instáveis.

Abstract Background Many clinical studies have confirmed that legumain is closely related to atherosclerosis. Unfortunately, different conclusions have been reached, and analyses and studies on atherosclerotic plaque characteristics in patients with increased plasma levels of legumain are still lacking. Objectives This study aimed to investigate the correlation between legumain and coronary atherosclerotic plaque characteristics. Methods A total of 81 patients with coronary atherosclerotic heart disease (CHD), including 43 patients with unstable angina (UA) and 38 patients with stable angina (SA), were screened by coronary angiography. Intravascular ultrasound (IVUS) was performed to evaluate the characteristics of coronary atherosclerotic plaques, and plasma legumain levels were also measured. Values of p < 0.05 were considered significant. Results Legumain concentration was significantly higher in the two CHD subgroups than in the control group (all p<0.001). Legumain concentrations in the UA group were significantly higher than in the SA group (p=0.001). The plaque area, remodeling index (RI), and eccentricity index (EI) in the UA group were significantly higher than those in the SA group (p<0.001, p=0.001, p=0.001, respectively). There was a significant positive correlation between legumain levels and RI and EI in both UA and SA patients (all p<0.05). Conclusions High plasma levels of legumain were closely related to the occurrence and severity of CHD, and the lesions tended to be unstable. Legumain is expected to be a potential inflammatory biomarker for the diagnosis of CHD and the early identification of unstable coronary lesions.

Maxent modeling for predicting the global potential distribution of talaromycosis marneffei / 中国热带医学

@#Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

Diagnostic value of heparin-binding protein in the cerebrospinal fluid for purulent meningitis in children

This study aimed to investigate the diagnostic value of heparin-binding protein (HBP) in the cerebrospinal fluid of children with purulent meningitis (PM). This study included 118 children with PM diagnosed at our hospital from January 2018 to January 2020, 110 children with viral meningitis (VM) and 80 children with suspected meningitis who were ruled out by cerebrospinal fluid (CSF) analysis during the same period. HBP and white blood cell (WBC) count in the CSF, and inflammatory factors, including C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and procalcitonin (PCT), were measured. Receiver-operator characteristic curves were used to analyze the predictive value of HBP, CRP, PCT, and TNF-α levels in the diagnosis of PM by CSF analysis. HBP levels in the CSF of children with PM were higher, while the CRP and serum PCT and TNF-α levels were elevated in all groups (P<0.05). In addition, HBP levels in the CSF were more accurate for the diagnosis of PM than traditional diagnostic indexes. HBP levels in the CSF can be used as an important reference for early diagnosis of PM.

Alveolar crest and relevant analysis of labial side of anterior teeth on skeletal Angle class III patients / 北京大学学报(医学版)

OBJECTIVE@#To measure the distance from cemento-enamel junction (CEJ) to alveolar crest (AC) of labial side of anterior teeth on skeletal Angle class III patients under direct vision during periodontal bone augmentation surgery and to make relevant analysis to find the relevant factors.@*METHODS@#In the study, 46 skeletal Angle class III patients (10 males and 36 females) received periodontal bone augmentation surgery of anterior teeth were included, with 67 jaws (27 maxillae and 40 mandibles) and 400 anterior teeth (161 maxillary anterior teeth and 239 mandibular anterior teeth). The mean age was 23.65 years. Maxillary anterior teeth consisted of 54 central incisors, 53 lateral incisors and 54 canines. Mandibular anterior teeth consisted of 79 central incisors, 80 lateral incisors and 80 canines. CEJ-AC was measured in three sites (mesial sites, central sites and distal sites) by Williams periodontal probes during periodontal bone augmentation surgery under direct vision by the same researcher.@*RESULTS@#The average CEJ-AC of 400 anterior teeth was (2.21±1.48) mm. The average CEJ-AC of maxillary anterior teeth was (1.72±1.13) mm, more than (2.54±1.60) mm of mandibular anterior teeth (P<0.05). The average CEJ-AC of canines was (2.42±1.78) mm, more than (2.06±1.27) mm of central incisors or (2.16±1.32) mm of lateral incisors (P<0.05). The average CEJ-AC of central sites was (3.04±2.01) mm, more than (1.79±0.86) mm of mesial sites or (1.81±0.89) mm of distal sites (P<0.05). CEJ-AC of 233 anterior teeth was more than 2 mm, accounting for 58.25%, and 117 anterior teeth with dehiscence were found, accounting for 29.25%. Multilevel and multivariate Logistic regression showed age, jaw, tooth and site were the relevant factors to the position of alveolar crest.@*CONCLUSION@#The position of alveolar crest of skeletal Angle class III patients who received periodontal bone augmentation surgery was lower than that of the general population, causing periodontal risks during decompensation orthodontics therapy before orthognathic surgery. The position of alveolar crest was lower in older patients than in younger patients, in mandibular teeth than in maxillary teeth, in canines than in central incisors or lateral incisors, and in central sites than in mesial sites or distal sites of labial side, which showed much higher risk.

Accuracy analysis of alveolar dehiscence and fenestration of maxillary anterior teeth of Angle class III by cone-beam CT / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the accuracy and reliability of detecting alveolar bone dehiscence and fenestration of maxillary anterior teeth of Angle class III by cone-beam computed tomography (CBCT).@*METHODS@#Eighteen Angle class III patients with 108 maxillary anterior teeth were included (3 males and 15 females) who accepted modified corticotomy in orthodontic therapy. The mean age was 23.6 years (18-30 years). The clinical detection of dehiscence and fenestration was done when modified corticotomy was performed by the same periodontist. The CBCT examination was conducted pre-operation and the detection of dehiscence and fenestration by CBCT was done by two periodontists. The data in modified corticotomy were used as the golden standard to calculate the parameters, such as sensitivity, specificity, positive and negative predictive values, Youden index (YI), positive and negative likelihood ratio. Kappa statistic was used to analyze the agreement between the clinical detection and the CBCT detection.@*RESULTS@#The incidence of dehiscence and fenestration was about 10.19% and 13.89% respectively, which mainly occurred on lateral incisors and canines. The median values of length and width of dehiscence were about 5 mm and 4 mm, and the median values of length and width of fenestration were 3 mm and 2 mm, respectively. Most fenestrations were detected on the middle third to the apical third of the root. For dehiscence, the agreement between clinical detection and CBCT detection was statistically significant (P<0.05). For fenestration, the agreement between clinical detection and CBCT detection was statistically significant (P<0.05). The values of sensitivity and specificity for detecting dehiscence were more than 0.7. The values of positive and negative predictive values for detecting dehiscence were 0.44 and 0.97. The values of sensitivity and specificity for detecting fenestration were 0.93 and 0.52. The values of positive and negative predictive values for detecting fenestration were 0.24 and 0.98.@*CONCLUSION@#For dehiscence, the agreement between clinical detection and CBCT detection was good. For fenestration, the agreement between clinical detection and CBCT detection was general. Detection of dehiscence and fenestration of maxillary anterior teeth of Angle class III by CBCT had limited diagnostic value in clinical practice with overestimation of dehiscence and fenestration incidence.

Inhibitory effect of tetramethylpyrazine preconditioning on overload training-induced myocardial apoptosis in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of tetramethylpyrazine (Tet) preconditioning on overload training-induced myocardial apoptosis in rats, and to explore cardioprotective mechanisms of Tet preconditioning.</p><p><b>METHODS</b>A total of 25 male Sprague-Dawley rats were randomly divided into three groups, including the control group (n=5), the overload training group (overload training for 8 weeks, n=10), and the Tet preconditioning group (Tet preconditioning for 8 weeks before overload training, n=10). After 8 weeks, cardiac structure and myocardial apoptosis were analyzed by histology, transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay staining. The expressions of Bcl-2, Bax, Caspase-3, and Caspase-9 in myocardium were evaluated by immunohistochemical staining.</p><p><b>RESULTS</b>Overload training caused swelling, disorder, partial rupture, and necrosis of myocardial focal necrotic fibers, as well as mitochondrial vacuolization, cristae rupturing, and blurring. In contrast, Tet preconditioning attenuated the swelling of myocardial fibers, decreased the amount of ruptured fibers, and inhibited mitochondrial vacuolization, resulting in clear cristae. Overload training significantly increased Bax expression and decreased Bcl-2/Bax ratio when compared with the control group (P<0.01). Conversely, Tet preconditioning significantly increased Bcl-2 expression and the Bcl-2/Bax ratio as compared with the overload training group (P<0.05). Overload training dramatically increased the expressions of Caspase-3 and Caspase-9 when compared with the control groupP<0.05). Following Tet preconditioning, the expression of Caspase-3 was significantly reduced compared with the overload training group (P<0.05), while Caspase-9 expression showed a slight decline (P>0.05).</p><p><b>CONCLUSION</b>Tet preconditioning increased the expression of Bcl-2 and reduced the expression of Caspase-3, thereby attenuating overload training-induced myocardial apoptosis, protecting against overload training-induced myocardial injury, and reducing damage to the myocardium due to overload training.</p>

Modeling and simulation activities to design sampling scheme for population pharmacokinetic study on amlodipine / 药学学报

Reasonable sampling scheme is the important basis for establishing reliable population pharmacokinetic model. It is an effective method for estimation of population pharmacokinetic parameters with sparse data to perform population pharmacokinetic analysis using the nonlinear mixed-effects models. We designed the sampling scheme for amlodipine based on D-optimal sampling strategy and Bayesian estimation method. First, optimized sample scenarios were designed using WinPOPT software according to the aim, dosage regimen and visit schedule of the clinical study protocol, and the amlodipine population model reported by Rohatagi et al. Second, we created a NONMEM-formatted dataset (n = 400) for each sample scenario via Monte Carlo simulation. Third, the estimation of amlodipine pharmacokinetic parameters (clearance (CL/F), volume (V/F) and Ka) was based on the simulation results. All modeling and simulation exercises were conducted with NONMEM version 7.2. Finally, the accuracy and precision of the estimated parameters were evaluated using the mean prediction error (MPE) and the mean absolute error (MAPE), respectively. Among the 6 schemes, schemes 6 and 3 have good accuracy and precision. MPE is 0.1% for scheme 6 and -0.6% for scheme 3, respectively. MAPE is 0.7% for both schemes. There is no significant difference in MPE and MAPE of volume among them. Therefore, we select scheme 3 as the final sample scenario because it has good accuracy and precision and less sample points. This research aims to provide scientific and effective sampling scheme for population pharmacokinetic (PK) study of amlodipine in patients with renal impairment and hypertension, provide a scientific method for an optimum design in clinical population PK/PD (pharmacodynamics) research.