Optimization of water extraction technology of Xiangqin jiere granules by orthogonal design based on G1-entropy weight compared with BP neural network / 中国药房

OBJECTIVE Optimizing the water extraction technology of Xiangqin jiere granules. METHODS The orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters. RESULTS The water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test. CONCLUSIONS The water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.

Clinical effects of iRoot BP plus and mineral trioxide aggregate in treatment of apical periodontitis with open apical permanent teeth / 口腔医学

Objective@#To analyze and evaluate the clinical application effect of bioceramic material mineral trioxide aggregate and iRoot BP plus on the formation of apical barrier in adult teeth with incomplete apical foramen.@*Methods@#A total of 200 permanent teeth with apical periodontitis whose apical foramen were not closed were randomly divided into two groups, and the apical barrier was prepared with MTA and iRoot BP plus, respectively. The operation time of MTA and iRoot BP plus and effects of different types of apical foramen destruction, lesion range of apical area, the filling of apical area and patients' age on the treatment success rate was analyzed and compared. @*Results@#The operation time of preparing apical barrier in iRoot BP plus group was shorter than that in MTA group, and the difference was statistically significant (P<0.05). However, different types of apical foramen destruction, lesion scope of apical area, filling of apical area and patients' age had no effect on the treatment success rate of the two groups (P>0.05). @*Conclusion@#The clinical effects of MTA and iRoot BP plus in the treatment of apical periodontitis of permanent teeth with unclosed apical foramen are similar, but the operation performance of iRoot BP plus is better.

Risk predictive models of healthcare-seeking delay among imported malaria patients in Jiangsu Province based on the machine learning / 中国血吸虫病防治杂志

Objective To create risk predictive models of healthcare-seeking delay among imported malaria patients in Jiangsu Province based on machine learning algorithms, so as to provide insights into early identification of imported malaria cases in Jiangsu Province. Methods Case investigation, first symptoms and time of initial diagnosis of imported malaria patients in Jiangsu Province in 2019 were captured from Infectious Disease Report Information Management System and Parasitic Disease Prevention and Control Information Management System of Chinese Center for Disease Control and Prevention. The risk predictive models of healthcare-seeking delay among imported malaria patients were created with the back propagation (BP) neural network model, logistic regression model, random forest model and Bayesian model using thirteen factors as independent variables, including occupation, species of malaria parasite, main clinical manifestations, presence of complications, severity of disease, age, duration of residing abroad, frequency of malaria parasite infections abroad, incubation period, level of institution at initial diagnosis, country of origin, number of individuals travelling with patients and way to go abroad, and time of healthcare-seeking delay as a dependent variable. Logistic regression model was visualized using a nomogram, and the nomogram was evaluated using calibration curves. In addition, the efficiency of the four models for prediction of risk of healthcare-seeking delay among imported malaria patients was evaluated using the area under curve (AUC) of receiver operating characteristic curve (ROC). The importance of each characteristic was quantified and attributed by using SHAP to examine the positive and negative effects of the value of each characteristic on the predictive efficiency. Results A total of 244 imported malaria patients were enrolled, including 100 cases (40.98%) with the duration from onset of first symptoms to time of initial diagnosis that exceeded 24 hours. Logistic regression analysis identified a history of malaria parasite infection [odds ratio (OR) = 3.075, 95% confidential interval (CI): (1.597, 5.923)], long incubation period [OR = 1.010, 95% CI: (1.001, 1.018)] and seeking healthcare in provincial or municipal medical facilities [OR = 12.550, 95% CI: (1.158, 135.963)] as risk factors for delay in seeking healthcare among imported malaria cases. BP neural network modeling showed that duration of residing abroad, incubation period and age posed great impacts on delay in healthcare-seek among imported malaria patients. Random forest modeling showed that the top five factors with the greatest impact on healthcare-seeking delay included main clinical manifestations, the way to go abroad, incubation period, duration of residing abroad and age among imported malaria patients, and Bayesian modeling revealed that the top five factors affecting healthcare-seeking delay among imported malaria patients included level of institutions at initial diagnosis, age, country of origin, history of malaria parasite infection and individuals travelling with imported malaria patients. ROC curve analysis showed higher overall performance of the BP neural network model and the logistic regression model for prediction of the risk of healthcare-seeking delay among imported malaria patients (Z = 2.700 to 4.641, all P values < 0.01), with no statistically significant difference in the AUC among four models (Z = 1.209, P > 0.05). The sensitivity (71.00%) and Youden index (43.92%) of the logistic regression model was higher than those of the BP neural network (63.00% and 36.61%, respectively), and the specificity of the BP neural network model (73.61%) was higher than that of the logistic regression model (72.92%). Conclusions Imported malaria cases with long duration of residing abroad, a history of malaria parasite infection, long incubation period, advanced age and seeking healthcare in provincial or municipal medical institutions have a high likelihood of delay in healthcare-seeking in Jiangsu Province. The models created based on the logistic regression and BP neural network show a high efficiency for prediction of the risk of healthcare-seeking among imported malaria patients in Jiangsu Province, which may provide insights into health management of imported malaria patients.

Research progress in correlation between insulin-like growth factor 2 mRNA binding protein 2 gene and type 2 diabetes mellitus / 中国生物制品学杂志

@#Type 2 diabetes mellitus(T2DM)was a chronic,non-communicable disease with a combination of multiple genetic and environmental factors,of which the main characteristics included insufficient insulin secretion and insulin resistance.Insulin-like growth factor 2 mRNA binding protein 2(IGF2BP2/IMP2),an important insulin secretion-related protein in human body,is mainly expressed in tissues and cells such as pancreas,fat and intestine.It has been confirmed that IGF2BP2 can down-regulate the expression of IGF2 and the function damage of the related islet β cell is an important cause of T2DM and vascular complications.Therefore,IGF2BP2 gene can be used as an important predictor for diabetes mellitus risk.This paper reviews the correlation between IGF2BP2 gene and T2DM.

Research progress of taste masking and evaluation technology of medicine / 中国药科大学学报

@#Most drugs taste bitter and irritating, resulting in poor compliance of patients, and the bad odor affects the therapeutic effect. The successful research and development of a drug should not only conform to the five quality characteristics of effectiveness, stability, safety, uniformity and economy, but also the compliance of patients to drugs with bad odor. The development of taste masking techniques is critical for bitter drugs.This review describes the principles, advantages and drawbacks of traditional taste masking techniques, and introduces the mechanism and application of novel taste masking techniques, such as melt granulation, hot melt extrusion, 3D printing, drug complex preparation, and bitter taste inhibitors. The in vitro evaluation methods of drug taste masking effect, such as functional magnetic resonance imaging, in vitro dissolution, and electronic tongue technology, are described. And introduce in vivo evaluation methods, such as animal and human taste, in the field of taste masking effect. A new strategy of BP neural network prediction model for drug taste evaluation is proposed, with a view to providing theoretical reference for the future research on drug taste masking.

4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.

An Atrial Fibrillation Classification Method Study Based on BP Neural Network and SVM / 中国医疗器械杂志

Atrial fibrillation is a common arrhythmia, and its diagnosis is interfered by many factors. In order to achieve applicability in diagnosis and improve the level of automatic analysis of atrial fibrillation to the level of experts, the automatic detection of atrial fibrillation is very important. This study proposes an automatic detection algorithm for atrial fibrillation based on BP neural network (back propagation network) and support vector machine (SVM). The electrocardiogram (ECG) segments in the MIT-BIH atrial fibrillation database are divided into 10, 32, 64, and 128 heartbeats, respectively, and the Lorentz value, Shannon entropy, K-S test value and exponential moving average value are calculated. These four characteristic parameters are used as the input of SVM and BP neural network for classification and testing, and the label given by experts in the MIT-BIH atrial fibrillation database is used as the reference output. Among them, the use of atrial fibrillation in the MIT-BIH database, the first 18 cases of data are used as the training set, and the last 7 cases of data are used as the test set. The results show that the accuracy rate of 92% is obtained in the classification of 10 heartbeats, and the accuracy rate of 98% is obtained in the latter three categories. The sensitivity and specificity are both above 97.7%, which has certain applicability. Further validation and improvement in clinical ECG data will be done in next study.

Comparison of the effect of iRoot BP Plus and MTA on direct pulp capping of carious pulp exposed mature permanent teeth / 口腔疾病防治

Objective@#To study the clinical efficacy of biological ceramics (iRoot BP Plus ) and mineral trioxide aggregate (MTA) in direct pulp capping of mature permanent teeth, to provide referrence for clinical application.@* Methods @# Seventy-four patients with pulp exposure due to deep caries or reversible pulpitis in 75 mature permanent teeth were selected and were randomly divided into two groups. iRoot BP Plus were used as pulp capping agents in the treatment group and MTA were used as pulp capping agents in the control group respectively. The clinical efficacy and imaging analysis were performed at 1, 3, 6 and 12 months after operation. Treatment success rate of the two groups were calculated, and the influence of various factors including gender, age, tooth position, cavity, number and size of pulp exposure on the efficacy of direct pulp capping were analyzed. @* Results @#Sixty patients with 61 mature permanent teeth were selected. Twelve mouths after treatment, 61 teeth of 60 patents were completely investigated (iRoot group: 31 teeth 30 patients; MTA group: 30 teeth 30 patients). The success rates of the 2 groups were 90.3% (iRoot BP Plus) and 90.0% (MTA), respectively. There was no statistical difference between 2 groups (P>0.05). Statistical analysis also showed that gender, age, tooth position, cavity, number and size of pulp exposure had no significant difference between the two groups (P>0.05). @*Conclusion@# Both iRoot BP Plus and MTA are effective in direct pulp capping of mature permanent teeth with carious pulp exposure, while the operation of iRoot is simple and convenient.

Prediction of CW chord after cataract surgery from IOL Master 700 measurement data based on SVR algorithm and BP neural network / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the changes in the Chang-Warning chord(CW chord)before and after cataract surgery using the IOL Master 700 and predict the CW chord using an artificial intelligence prediction model and preoperative measurement data.METHODS: The analysis was conducted on the preoperative and postoperative IOL Master 700 measurements of 304 cataract patients. This included astigmatism vector value, average keratometry, axial length, anterior chamber depth, lens thickness, corneal central thickness, white-to-white, the position of the Purkinje reflex I image relative to the corneal center and pupil center, and the CW chord. A prediction model based on the SVR algorithm and the BP neural network algorithm was established to predict the postoperative CW chord using the preoperative CW chord and ocular biological parameters.RESULTS: The X component of the CW chord showed a slight shift in the temporal direction in both the left and right eyes after cataract surgery, while the Y component changed little. The SVR model, using the preoperative CW chord and other preoperative biometric parameters as input data, was able to predict the X and Y components of the CW chord more accurately than the BP neural network.CONCLUSION: The CW chord can be directly measured with a coaxial fixation light using various biometers, corneal topographers, or tomographers. The use of the SVR algorithm can accurately predict the postoperative CW chord before cataract surgery.

A clinical analysis of 74 cases of bullous pemphigoid with stroke / 中华皮肤科杂志

Objective:To investigate differences in clinical characteristics between bullous pemphigoid (BP) patients with stroke and those without, and their relationship with the prognosis of stroke.Methods:A retrospective analysis was performed on medical records of 330 BP inpatients in the First Affiliated Hospital of Zhengzhou University from September 2012 to April 2020. These patients were divided into BP + stroke (ST) group and BP - ST group according to whether they were accompanied by stroke, and clinical manifestations and relevant laboratory examination results were compared between the two groups. According to the stroke outcome score assessed by modified Rankin Scale (mRS), patients in the BP + ST group were further divided into good-prognosis ST group (mRS ≤ 2 points) and poor-prognosis ST group (mRS > 2 points), and subgroup analysis was conducted. Correlations between measurement data (such as age, disease course and laboratory examination results) and mRS scores were analyzed.Results:In the BP - ST group (256 cases), 151 were males and 105 were females, and their age ranged from 19 to 92 (66.8 ± 13.6) years; in the BP + ST group (74 cases), 45 were males and 29 were females, and their age ranged from 48 to 92 (74.6 ± 9.6) years; Compared with the BP - ST group, the BP + ST group showed older age ( t = -5.57, P < 0.001), shorter disease course of BP ( Z = -3.07, P = 0.002), and higher anti-BP180 IgG antibody levels (215.0 [157.2, 283.1] U/ml vs. 155.0 [63.9, 279.8] U/ml; Z = -2.12, P = 0.034). The distribution of skin lesions significantly differed between the two groups ( χ2 = 10.51, P = 0.015), and the BP + ST group showed a significantly lower proportion of patients with generalized lesions ( P<0.05), but a higher proportion of patients with lesions on the limbs ( P<0.05). Subgroup analysis showed significant differences in the patients′ age, BP course, lesion distribution and anti-BP180 IgG antibody levels among the good-prognosis ST group, poor-prognosis ST group and BP - ST group ( F = 10.83, P<0.001; Z = 17.24, P<0.001; χ2 = 15.57, P = 0.026; Z = 6.29, P = 0.043, respectively). There was no significant difference in the age between the good-prognosis ST group and poor-prognosis ST group (adjusted P = 1.000), but the patients were significantly older in the two above groups than in the BP - ST group (adjusted P = 0.001, 0.007, respectively) ; the poor-prognosis ST group showed significantly shorter BP courses (adjusted P = 0.016, < 0.001, respectively) and a higher proportion of patients with lesions on the limbs (both P < 0.05) compared with the good-prognosis ST group and BP - ST group, and significantly higher serum anti-BP180 IgG antibody levels compared with the BP - ST group (226.2 [163.6, 285.8] U/ml vs. 155.0 [63.9, 279.8] U/ml; adjusted P = 0.037). There were no significant differences in the gender distribution, lesional morphology, percentages and counts of peripheral blood eosinophils, serum total IgE levels, and anti-BP230 IgG antibody levels between the BP + ST group and BP - ST group (all P > 0.05), or among the good-prognosis ST group, poor-prognosis ST group and BP - ST group (all P > 0.05). Correlation analysis in the BP + ST group showed a significantly negative correlation between the BP course and mRS scores ( r = -0.33, P = 0.004), and a significantly positive correlation between the anti-BP180 IgG antibody levels and mRS scores ( r = 0.34, P = 0.032) . Conclusion:There were differences in the patients′ age, BP course, lesion distribution, and anti-BP180 IgG antibody levels between the BP patients with stroke and those without, and the differences were more obvious between the poor-prognosis ST group and BP - ST group.

Role of ambulatory blood pressure monitoring in hypertensive patients having controlled office blood pressure

Background and objectives: Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In this study we tried to know the role of office and ambulatory BP in treated hypertensive patients. Methods and patients: Prospective cohort of 561 treated hypertensive patients were enrolled in the study. Hypertension definitions were according to JNC 8 classification. Office BP and ambulatory BP monitoring was done according to defined protocol. Results: From a subgroup of 158 treated hypertensive patients, 91(16.2%) patients were having white coat hypertension (p value 0.00 by Pearson chi square test). In a subset of 403 patients who were having controlled BP on the day of enrolment as well as on the day of attaching ambulatory BP monitor; 98 (17.4%) patients were having masked uncontrolled hypertension (MUCH). In addition there was very significant percentage of non-dippers and reverse dippers. In our study we found that office BP has a moderate to low specificity and sensitivity and low negative predictive value for overall control in treated hypertensive patients. Conclusion: Ambulatory BP monitoring should be included in the management protocol of treated hypertensive patients, for the optimal BP control.

A More Hygienic Method for Measuring Blood Pressure

Background : Blood Pressure (BP) measurement is the commonest test performed in any healthcare facility. The same BP cuff is used for measurement of BP in many patients. The BP cuff can get contaminated with microorganisms1. It may become a vector in transmission of communicable and infectious diseases. The Corona Pandemic has highlighted the needs to prevent transmission of infections by taking precautions in health care facilities. Disposable BP cuffs are available in Western Countries. Though they solve the contamination problem effectively, they are very expensive. To overcome the problem of contamination of the BP cuff, we propose to use a very thin plastic paper to cover the arm of the patient, to tie the BP cuff on the plastic paper so that the cuff does not come in contact with the patient’s body. Aim : To validate the accuracy of the BP measured after tying the cuff in such non contact manner. Settings and Design: The study was carried out at Dr Rajeev Raut Eye Clinic with consent obtained from Ethics Committee. 50 patients underwent BP measurement in supine position with and without the plastic wrap around the arm. The results of BP measurements thus obtained were statistically analysed. Results : The BP measurement obtained with the wrap and without the wrap were not found to be statistically significantly different. Conclusions : The BP measurements obtained using a Polyvinyl Chloride (PVC) cling film wrap covering the arm are similar to those obtained without the use of the wrap. However, further studies are needed to prove the reduction in contamination rate.

Regulatory role of circIGF2BP3 in autophagy in photoaged dermal fibroblasts / 中华皮肤科杂志

Objective:To preliminarily investigate the effect of circIGF2BP3 on autophagy in photoaged dermal fibroblasts.Methods:Human dermal fibroblasts were isolated from circumcised foreskin tissues from 6 children in the Department of Urological Surgery, Third Affiliated Hospital of Sun Yat-sen University. An ultraviolet A (UVA) -induced photoaged human dermal fibroblast model (UVA radiation group) was established by repeated UVA radiation at a dose of 10 J/cm 2 for 14 consecutive days, and human dermal fibroblasts receiving no treatment served as control group. The photoaged cell model was verified by β-galactosidase staining, Western blot analysis for determining P21 protein expression, and cell counting kit-8 (CCK8) assay for evaluating cell viability. Moreover, Western blot analysis was performed to determine the protein expression of autophagy-related proteins P62, microtubule-associated protein 1 light chain 3 (LC3) -Ⅰand LC3-Ⅱ in photoaged human dermal fibroblasts, and real-time quantitative RCR (qRT-PCR) to verify the differential expression of circIGF2BP3 between photoaged and normal human dermal fibroblasts. Furthermore, circIGF2BP3 was biologically annotated. Some cultured primary human dermal fibroblasts were divided into 4 groups: empty vector group transfected with an empty vector, UVA + empty vector group transfected with an empty vector followed by repeated UVA radiation, circIGF2BP3 group transfected with a circIGF2BP3-overexpressing lentiviral vector, UVA + circIGF2BP3 group transfected with a circIGF2BP3-overexpressing lentiviral vector followed by repeated UVA radiation. Western blot analysis was performed to determine the expression of autophagy-related proteins. Statistical analysis was carried out by using t test, one-way analysis of variance and least significant difference- t test. Results:Compared with the control group, the UVA radiation group showed significantly increased proportions of β-galactosidase-positive cells (61.33% ± 5.78% vs. 6.37% ± 0.32%, t = 9.49, P < 0.01) and P21 expression (1.25 ± 0.03 vs. 1.00 ± 0.05, t = 4.26, P < 0.05), but significantly decreased cell viability (74.33% ± 3.48% vs. 100%, t = 7.38, P < 0.01). Moreover, the P62 expression and LC3-Ⅱ/Ⅰ ratio were significantly higher in the UVA radiation group than in the control group (both P < 0.05). The relative expression of circIGF2BP3 was 0.72 ± 0.04 in the photoaged human dermal fibroblasts, which was significantly lower than that in the normal human dermal fibroblasts (1.00 ± 0.03, t = 5.46, P < 0.01). The P62 expression and LC3-Ⅱ/Ⅰ ratio were significantly lower in the circIGF2BP3 group (0.60 ± 0.01, 0.71 ± 0.01, respectively) than in the empty vector group (1.00 ± 0.02, 1.00 ± 0.01, t = 16.25, 2.75, P < 0.01, < 0.05, respectively), and lower in the UVA + circIGF2BP3 group (1.05 ± 0.02, 2.04 ± 0.05, respectively) than in the UVA + empty vector group (1.31 ± 0.02, 2.72 ± 0.14, t = 10.493, 6.472, respectively, both P < 0.01) . Conclusion:circIGF2BP3 can regulate autophagy in UVA-induced photoaged dermal fibroblasts, which provides a new potential therapeutic target for the prevention and treatment of skin photoaging.

ZNF451 promotes DNA damage repair by recruiting 53BP1/MDC1 in A549 and HeLa cells / 中华放射医学与防护杂志

Objective:To investigate the role of SUMO E3 ligase ZNF451 in DNA damage repair and explore the underlying mechanism in non-small cell lung cancer A549 cells and cervical cancer HeLa cells.Methods:A549 cells and HeLa cells were irradiated with γ-ray irradiation or treated with etoposide. Cell proliferation viability was detected by the cell counting kit-8 assay. Protein expression was detected by Western blot assay. DNA damage repair level was detected by DR-GFP plasmid system, and the spatial positioning was detected by immunofluorescence.Results:Etoposide decreased the expression level of ZNF451 in a dose- and time- dependent manner. After treatment with 30, 50, 80 μmol/L etoposide, the cell viability were reduced after the knockdown of ZNF451 in A549 and HeLa cells(A549: t = 27.62, 25.61, 5.32, P<0.01; HeLa: t = 30.77, 21.28, 4.18, P<0.01). Furthermore, ZNF451 was recruited at DNA damage sites. A co-localization and endogenous interaction were found between ZNF451 and γ-H2AX after the treatment of irradiation or etoposide. Moreover, the expression level of γ-H2AX was significantly increased after treatment with 30, 50, 80 μmol/L etoposide(A549: t = 6.12, 10.67, 4.68, P<0.01; HeLa: t = 7.94, 9.81, 15.12, P<0.01)and the repair efficiency of NHEJ was reduced in ZNF451 knockdown cells( t = 18.60, P<0.05). Finally, the immunofluorescence assay showed that ZNF451 was co-localizated with 53BP1 and MDC1 after irradiation or etoposide treatment. Conclusions:Knockdown of ZNF451 inhibits cell proliferation and increases the level of DNA damage in A549 and HeLa cells. ZNF451 was recruited to DNA damage sites after DSBs and participated in NHEJ repair by co-localizing with DNA damage repair factor 53BP1/MDC1.

The study on inflammatory mechanism of cognitive dysfunction induced by 1-bromopropane in rats / 中华行为医学与脑科学杂志

Objective:To observe the role of neuroinflammation in cognitive dysfunction induced by 1-bromopropane (1-BP) in rats.Methods:Male Wistar rats were randomly divided into control group, 1-BP group, pyrrolidine dithiocarbamate(PDTC)+ 1-BP group and PDTC group, with 15 rats in each group. Rats in 1-BP group and PDTC+ 1-BP group were given 800 mg / kg 1-BP by gavage, and rats in control group and PDTC group were given equal volume corn oil once a day for 12 days; rats in PDTC group and PDTC+ 1-BP group were intraperitoneally injected with 100 mg / kg PDTC 30 minutes after gavage, while rats in control group and 1-BP group were injected with equal volume of normal saline once a day for 12 days.From the 7th to 12th day of the experiment, ten rats in each group were randomly selected and subjected to Morris water maze test for detect the cognitive function. In the positioning navigation test, the learning ability of rats was evaluated by the escape latency and total swimming distance respectively. In the space exploration experiment, the memory ability of experimental animals was evaluated by the number of times crossing the target platform. After the experiment, ten rats were sacrificed, the cerebral prefrontal cortex was harvested. The cytosolic and nuclear NF-κB expression and phosphorylation were detected by Western blot, the mRNA levels of TNF-α and IL-1β were detected by qRT-PCR. After cardiac perfusion fixation, the brains of 5 rats were taken to make frozen sections for immunohistochemical staining and Nissl staining. SPSS 20.0 software was used for statistical analysis, repetitive measurement deviation analysis was used for the analysis of the swimming distance and the escape latency in positioning navigation test, One-way ANOVA was used for the analysis of the number of times crossed the target platform in spatial probe test and other data. Tukey's test was used for Post hoc comparison.Results:The results of Morris water maze showed that there was significant interaction between group and training time in the total swimming distance of rats in the four groups ( F=3.762, P<0.05). Simple effect analysis showed that the total swimming distance of 1-BP group in 1-4 days were longer than those of control group (all P<0.05), while the total swimming distance of PDTC+ 1-BP group in 1-4 days were shorter than those of 1-BP group (all P<0.05). There was significant interaction between group and training time in the escape latency among the four groups ( F=6.541, P<0.01). The escape latencies of 1-BP group in 1-4 days were longer than those of control group (all P<0.05), while the escape latencies of PDTC+ 1-BP group in 1-4 days were shorter than those of 1-BP group (all P<0.05). The results of space exploration experiment showed that there was significant difference in the number of crossing the platform among the four groups ( F=75.333, P<0.01). The number of crossing the platform (1.08±0.29) in 1-BP group was lower than that in the control (3.35±0.05) ( P<0.01). The number of crossing the platform (1.95±0.26) in PDTC+ 1-BP group was higher than that in 1-BP group ( P<0.01). It had significant difference both in the cytoplasm and in the nucleus of the NF-κB protein level in prefrontal cortex among rats of the four groups ( F=20.865, 23.877, both P<0.01). The levels of NF-κB in cytoplasm and nucleus of rats in 1-BP group were both higher than those in control group (cytoplasm: (177.3±32.1)%, (100.0±8.4)%, P<0.01; nucleus: ( 173.2±27.1)%, (100.0±8.4)%, P<0.01). While the levels of NF-κB in cytoplasm and nucleus of 1-BP+ PDTC group were both lower than those of 1-BP group (cytoplasm: (148.7±22.0)%, (177.3±32.1)%, P<0.01; nucleus: (149.7±18.8)%, (173.2±27.1)%, P<0.01). The results of qRT-PCR showed that there were significant differences in the mRNA levels of TNF-α and IL-1β in the prefrontal cortex among the four groups ( F=17.464, 17.382, both P<0.01). The levels of TNF-α and IL-1β mRNA in 1-BP group were higher than those in control group (both P<0.05), and the levels of TNF-α and IL-1β mRNA in PDTC+ 1-BP group were both lower than those in 1-BP group (both P<0.05). The results of immunohistochemistry showed that compared with the control group, the number of microglia and astrocytes in the 1-BP group increased (microglia: (158.30±9.68), (110.20±16.30), P<0.05; astrocytes: (122.76±4.35), (80.24±6.96), P<0.05), and the morphology was also activated, with light staining and reduced number of Nissl bodies in neurons.The number of microglia and astrocytes in PDTC + 1-BP group was lower than that in 1-BP group (microglia: (131.70±14.67), (158.30±9.68), P<0.05; astrocytes: (101.54±4.55), (122.76±4.35), P<0.05), and the Nissl body staining of neurons was significantly deepened. Conclusion:NF-κB signaling pathway might be the key mechanism of 1-BP neurotoxicity. PDTC intervention could significantly improve the neuroinflammatory response and behavioral disorders of experimental animals intoxicated with 1-BP.

Role and mechanism of IGF2BP3 in malignant transformation of human gastric epithelial cells induced by MNNG / 环境与职业医学

Background N6-methyladenosine (m6A) RNA methylation may play an important role in the process of malignant transformation of cells induced by environmental carcinogens. However, the specific roles and mechanisms need to be further explored. Objective To explore the role and mechanism of m6A binding protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the malignant transformation of human gastric mucosal epithelial cells GES-1 induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods Based on the GES-1 malignant transformation cells MC-30, a stable knockdown IGF2BP3 MC-30 cell line (MC30-shIGF2BP3, abbreviated as MC30-shI3) was constructed by lentiviral transfection technology, and a negative control group (MC30-NC) was also prepared. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were applied to detect the mRNA expression and protein levels of IGF2BP3. RNA binding protein immunoprecipitation (RIP-qPCR) was used to examine the combination between IGF2BP3 protein and MYC mRNA in malignant cells MC-30. Furthermore, the stability of MYC mRNA was detected by actinomycin D assay. CCK-8 and Transwell respectively were employed to detect cell proliferation, migration, and invasion. Western blotting was applied to detect the expression of EMT markers (N-cadherin, Vimentin, α-SMA, and Snail). The role of the downstream target gene MYC was further elucidated by a rescue assay in MC30-shI3 cells transfected with a plasmid overexpressing MYC to observe changes in cellular phenotypes (proliferation, migration, invasion) and expression of key EMT proteins. Results Compared with the control group, the expression of IGF2BP3 mRNA was up-regulated after 5, 10, 20, and 40 μmol·L−1 MNNG infection of GES-1 cells (P<0.05). After 20 μmol·L−1 MNNG infection, the expression level of IGF2BP3 mRNA increased with prolongation of exposure time (P<0.05). Compared with the control group, the mRNA and protein expression levels of IGF2BP3 were up-regulated in the 10th, 20th, and 30th generations of 5 μmol·L−1 MNNG malignant transformation (P<0.05). The results of qRT-PCR and Western blotting showed that, compared with the MC30-NC group, the IGF2BP3 and MYC mRNA expression and protein expression decreased in the MC30-shI3 group (P<0.01). The CCK8 and transwell assay results showed that, compared with the MC30-NC group, the cell proliferation, migration, and invasion abilities significantly reduced in the MC30-shI3 group (P<0.01). The results of the Western blotting showed that, compared with the MC30-NC group, the protein levels of EMT markers N-cadherin, Vimentin, α-SMA, and Snail decreased in the MC30-shI3 group (P<0.01). The results of RIP-qPCR showed that, compared with the IgG group, the mRNA level was higher for the enriched MYC in the IGF2BP3 group (P<0.01); the results of the actinomycin D assay showed that, compared with the MC30-NC group, the stability of MYC mRNA significantly reduced in the MC30-shI3 group (P<0.01). While the rescue experiment showed that, compared with the IGF2BP3 knock-down+vector group, the MYC protein level significantly increased in the IGF2BP3 knock-down + MYC over-expression group (P<0.01), the proliferation, migration, and invasion abilities significantly enhanced (P<0.01), and the EMT key proteins (N-cadherin, Vimentin, α-SMA, Snail) increased in the MC30-shI3+MYC group (P<0.01). Conclusion Exposure to MNNG could result in up-regulation of IGF2BP3 expression in GES-1 cells. IGF2BP3 may enhance the proliferation, migration, and invasion of malignantly transformed human gastric epithelial cells by binding to MYC mRNA and increasing its stability and expression level and thus promoting the EMT process, which in turn affects the progression of malignant transformation.

Comparison of the predictive performance of Logistic regression, BP neural network and support vector machine model for the risk of acute exacerbation of readmission in elderly patients with chronic obstructive pulmonary disease within 30 days / 中华危重病急救医学

Objective:To compare the effectiveness of Logistic regression, BP neural network and support vector machine models in the prediction of 30-day risk of readmission in elderly patients with an exacerbation of chronic obstructive pulmonary disease (COPD) and to provide a scientific basis for the screening and prevention of high-risk patients with readmission.Methods:The COPD patient survey questionnaire was made, including the general data questionnaire, modified Medical Research Council dyspnea scale (mMRC), activities of daily living (ADL), the geriatric depression scale, the mini nutritional assessment-short form (MNA-SF) and COPD assessment test (CAT). Elderly COPD patients were selected from the department of respiratory medicine of 13 general hospitals in Ningxia from April 2019 to August 2020 by convenience sampling method, and they were followed up 30 days after discharge. To explore the risk factors of patient readmission, Logistic regression model, BP neural network model and support vector machine models were constructed based on the risk factors. According to the ratio of the training set to the testing set of 7∶3, the model was divided into the training set sample and the testing set sample. The prediction efficiency of the model was compared by the precision rate, recall rate and accuracy rate, F1 index and the area under the receiver operator characteristic curve (AUC).Results:A total of 1 120 patients were investigated, including 879 non-readmission patients and 241 readmission patients. Univariate regression analysis showed that there were statistically significant differences in age, education level, smoking status, proportion of diabetes and coronary heart disease, hospitalization times of acute exacerbation of COPD in the past 1 year, seasonal factors and long-term home oxygen therapy, regular medication, proportion of rehabilitation exercise, course of disease, ADL, depression status, mMRC, nutritional status between non-readmission patients and readmission patients. Binary Logistic regression analysis showed that education level, smoking status, coronary heart disease, hospitalization times of acute exacerbation of COPD in the past 1 year, seasonal factors, whether long-term home oxygen therapy, whether regular medication, nutritional status were the risk factors for 30-day acute exacerbation of readmission in elderly patients with COPD. The training set showed that the accuracy rate of Logistic regression model, BP neural network model and support vector machine models were 70.95%, 76.51% and 84.78%, respectively. The recall rates were 79.55%, 86.36% and 88.64%, respectively. The accuracy rates were 87.81%, 90.81% and 93.82%, respectively. F1 indexes were 0.75, 0.81 and 0.87, respectively. The AUC were 0.850, 0.893 and 0.921, respectively. The testing set showed that the precision rate of Logistic regression model, BP neural network model and support vector machine model were 78.38%, 80.65% and 88.57%, respectively. The recall rates were 70.73%, 60.98% and 75.61%, respectively. The accuracy rates were 85.82%, 84.40% and 90.07%, respectively. F1 indexes were 0.74, 0.69 and 0.82, respectively. The AUC were 0.814, 0.775 and 0.858, respectively.Conclusion:Comparing with Logistic regression and BP neural network, support vector machine model has better prediction effect, and can effectively predict the risk of acute exacerbation of readmission in elderly patients with COPD within 30 days.

Osteonecrosis de los maxilares asociada a drogas antirresortivas en pacientes osteoporóticos: presentación de un caso clínico / Antiresorptive drugs-related jaw osteonecrosis in osteoporotic patients: report of a clinical case

La osteoporosis se caracteriza por una masa ósea baja con deterioro de la microarquitectura del tejido que conduce a la fragilidad, lo que aumenta el riesgo de fracturas. Después de la menopausia, la deficiencia de estrógenos aumenta la exposición del tejido al ligan- do RANK, lo que resulta en un aumento de la reabsorción y pérdida ósea, que pueden provocar osteoporosis. (1) Los bifosfonatos y el denosumab son utilizados para el tratamiento de la osteoporosis debido a su capacidad anticatabólica, que reducen la remodelación previniendo la pérdida de masa ósea, disminuyendo la probabilidad de fracturas y aumentando la densidad mineral del tejido. (2) La osteonecrosis de los maxilares asociadas a drogas antirresortivas es una situación que se presenta en pacientes que consumen de manera crónica antirresortivos para el tratamiento de enfermedades como: osteoporosis, osteogénesis imperfecta, enfermedad de Paget, displasia fi- brosa, hipercalcemia maligna asociada a tratamiento oncológico (AU)

Osteoporosis is characterized by low bone mass with deterioration of the tissue microarchitec- ture leading to fragility, which increases the risk of fractures. After menopause, estrogen deficiency increases tissue exposure to the RANK ligand, resulting in increased bone loss and resorption, which can lead to osteoporosis. (1) Bisphosphonates and denosumab are used for the treatment in low concentration, due to their anticatabolic capacity, which reduce remodeling, preventing loss of bone mass and fractures besides, antiresorptives drugs increase the mineral density of the tissue. (2) Osteonecrosis of the jaw associated with antiresorptives drugs occurs in patients whose chro- nically consume these drugs for the treatment of diseases such as: osteoporosis, imperfect osteogenesis, Paget's disease, fibrous dysplasia, malignant hypercalcemia associated with oncological treatment (AU)

Hipertensão mascarada: qual a importância da mrpa neste contexto? / Masked hypertension: how important is hbpm in this context?

A hipertensão arterial (HA) é o principal fator contributivo para as doenças cardiovasculares, as quais constituem a mais importante causa de morte prevenível no mundo. A falta de conhecimento da população acerca da doença, e consequentemente de um diagnóstico adequado, torna baixo o número de pessoas que se tratam. O aspecto silencioso da HA, e a má adesão ao tratamento proposto, dentre outros fatores, contribuem para o elevado risco de complicações. A medida da pressão arterial (PA) neste contexto apresenta grande importância não apenas no diagnóstico, mas também no acompanhamento de portadores de HA, podendo ser realizada de forma casual, em consultório, ou fora do mesmo com a utilização de outros métodos para tal. Dentre as medidas de PA, a monitorização residencial da PA (MRPA) se destaca. É um método destinado a fazer registro da PA fora do ambiente de consultório, obedecendo a um protocolo previamente estabelecido e normatizado. Além disto, a MRPA apresenta custos menores do que a monitorização ambulatorial da PA (MAPA). De acordo com a atual Diretriz Brasileira de HA, são considerados anormais valores de PA consultório ≥ 140/90 mmHg e de MRPA ≥ 130/80 mmHg. Sob esta perspectiva, a MRPA é um exame que permite que se faça o diagnóstico de HA verdadeira (PA elevada no consultório e na MRPA), normotensão verdadeira (PA normal no consultório e na MRPA), HA do avental branco (HAB) (PA elevada no consultório e normal na MRPA) e HA mascarada (HM) (PA normal no consultório e elevada na MRPA). O diagnóstico de HM é bastante relevante na prática clínica, pois em termos prognósticos, a HM apresenta um risco cardiovascular maior que a HAB e a normotensão verdadeira. Além disto, a incidência de eventos cardiovasculares na HM é similar ou até superior à da HA verdadeira.

Hypertension is the main contributing factor to cardiovascular diseases, which are the most important cause of death in the world. The lack of proper diagnosis, mainly due to the silent aspect of hypertension, makes the rate of people undergoing treatment low, contributing to the high risk of complications. The measurement of blood pressure (BP) in this context is important not only in the diagnosis, but also in the follow-up of patients with hypertension, and it can be performed casually, in the office, or outside the office, using other methods for this purpose. Home blood pressure monitoring (HBPM) is a method designed to record BP outside the office environment, following a previously established and standardized protocol and has a lower cost than ambulatory blood pressure monitoring (ABPM) According to the current Brazilian hypertension guideline, office BP values ≥ 140/90 mmHg and HBPM values ≥ 130/80 mmHg are considered abnormal. From this perspective, HBPM is a test that allows the diagnosis of true hypertension (high BP in the office and in HMBP), true normotension (normal BP in the office and in the HBPM), white coat hypertension (high BP in the office and normal BP in HBPM) and masked hypertension (normal BP in the office and high in HBPM). The diagnosis of masked hypertension is quite relevant in clinical practice, because this phenotype has greater cardiovascular risk than true normotension and white coat hypertension. On the other hand, the incidence of cardiovascular events is similar or even greater in masked hypertension in comparison with true hypertension.

Proteomics-based identification of cancer-associated proteins in chronic lymphocytic leukaemia

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a neoplasm of B-cells characterized by variable prognosis. Exploring the proteome of CLL cells may provide insights into the disease. Therefore, eleven proteomics experiments were conducted on eleven primary CLL samples. RESULTS: We reported a CLL proteome consisting of 919 proteins (false discovery rate (FDR) 1%) whose identification was based on the sequencing of two or more distinct peptides (FDR of peptide sequencing 1%). Mass spectrometry-based protein identification was validated for four different proteins using Western blotting and specific antibodies in different CLL samples. Small sizes of nucleolin (~57 kDa and ~68 kDa) showed a potential association with good prognosis CLL cells (n = 8, p < 0.01). Compared with normal B-cells, CLL cells over-expressed thyroid hormone receptor-associated protein 3 (THRAP3; n = 9; p = 0.00007), which is implicated in cell proliferation; and heterochromatin protein 1-binding protein 3 (HP1BP3; n = 10; p = 0.0002), which promotes cell survival and tumourogenesis. A smaller form of HP1BP3, which may correspond to HP1BP3 isoform-2, was specifically identified in normal B-cells (n = 10; p = 0.0001). HP1BP3 and THRAP3 predicted poor prognosis of CLL (p 0.05). Consistently, THRAP3 and HP1BP3 were found to be associated with cancer-related pathways (p 0.05). CONCLUSIONS: Our findings add to the known proteome of CLL and confirm the prognostic importance of two novel cancer-associated proteins in this disease.