[Preliminary study on automatic quantification and grading of leopard spots fundus based on deep learning technology].

Objective: To achieve automatic segmentation, quantification, and grading of different regions of leopard spots fundus (FT) using deep learning technology. The analysis includes exploring the correlation between novel quantitative indicators, leopard spot fundus grades, and various systemic and ocular parameters. Methods: This was a cross-sectional study. The data were sourced from the Beijing Eye Study, a population-based longitudinal study. In 2001, a group of individuals aged 40 and above were surveyed in five urban communities in Haidian District and three rural communities in Daxing District of Beijing. A follow-up was conducted in 2011. This study included individuals aged 50 and above who participated in the second 5-year follow-up in 2011, considering only the data from the right eye. Color fundus images centered on the macula of the right eye were input into the leopard spot segmentation model and macular detection network. Using the macular center as the origin, with inner circle diameters of 1 mm, 3 mm, and outer circle diameter of 6 mm, fine segmentation of the fundus was achieved. This allowed the calculation of the leopard spot density (FTD) and leopard spot grade for each region. Further analyses of the differences in ocular and systemic parameters among different regions' FTD and leopard spot grades were conducted. The participants were categorized into three refractive types based on equivalent spherical power (SE): myopia (SE<-0.25 D), emmetropia (-0.25 D≤SE≤0.25 D), and hyperopia (SE>0.25 D). Based on axial length, the participants were divided into groups with axial length<24 mm, 24-26 mm, and>26 mm for the analysis of different types of FTD. Statistical analyses were performed using one-way analysis of variance, Kruskal-Wallis test, Bonferroni test, and Spearman correlation analysis. Results: The study included 3 369 participants (3 369 eyes) with an average age of (63.9±10.6) years; among them, 1 886 were female (56.0%) and 1, 483 were male (64.0%). The overall FTD for all eyes was 0.060 (0.016, 0.163); inner circle FTD was 0.000 (0.000, 0.025); middle circle FTD was 0.030 (0.000, 0.130); outer circle FTD was 0.055 (0.009, 0.171). The results of the univariate analysis indicated that FTD in various regions was correlated with axial length (overall: r=0.38, P<0.001; inner circle: r=0.31, P<0.001; middle circle: r=0.36, P<0.001; outer circle: r=0.39, P<0.001), subfoveal choroidal thickness (SFCT) (overall: r=-0.69, P<0.001; inner circle: r=-0.57, P<0.001; middle circle: r=-0.68, P<0.001; outer circle: r=-0.72, P<0.001), age (overall: r=0.34, P<0.001; inner circle: r=0.30, P<0.001; middle circle: r=0.31, P<0.001; outer circle: r=0.35, P<0.001), gender (overall: r=-0.11, P<0.001; inner circle: r=-0.04, P<0.001; middle circle: r=-0.07, P<0.001; outer circle: r=-0.11, P<0.001), SE (overall: r=-0.20; P<0.001; inner circle: r=-0.19, P<0.001; middle circle: r=-0.20, P<0.001; outer circle: r=-0.20, P<0.001), uncorrected visual acuity (overall: r=-0.18, P<0.001; inner circle: r=-0.26, P<0.001; middle circle: r=-0.24, P<0.001; outer circle: r=-0.22, P<0.001), and body mass index (BMI) (overall: r=-0.11, P<0.001; inner circle: r=-0.13, P<0.001; middle circle: r=-0.14, P<0.001; outer circle: r=-0.13, P<0.001). Further multivariate analysis results indicated that different region FTD was correlated with axial length (overall: ß=0.020, P<0.001; inner circle: ß=-0.022, P<0.001; middle circle: ß=0.027, P<0.001; outer circle: ß=0.022, P<0.001), SFCT (overall: ß=-0.001, P<0.001; inner circle: ß=-0.001, P<0.001; middle circle: ß=-0.001, P<0.001; outer circle: ß=-0.001, P<0.001), and age (overall: ß=0.002, P<0.001; inner circle: ß=0.001, P<0.001; middle circle: ß=0.002, P<0.001; outer circle: ß=0.002, P<0.001). The distribution of overall (H=56.76, P<0.001), inner circle (H=72.22, P<0.001), middle circle (H=75.83, P<0.001), and outer circle (H=70.34, P<0.001) FTD differed significantly among different refractive types. The distribution of overall (H=373.15, P<0.001), inner circle (H=367.67, P<0.001), middle circle (H=389.14, P<0.001), and outer circle (H=386.89, P<0.001) FTD differed significantly among different axial length groups. Furthermore, comparing various levels of FTD with systemic and ocular parameters, significant differences were found in axial length (F=142.85, P<0.001) and SFCT (F=530.46, P<0.001). Conclusions: The use of deep learning technology enables automatic segmentation and quantification of different regions of theFT, as well as preliminary grading. Different region FTD is significantly correlated with axial length, SFCT, and age. Individuals with older age, myopia, and longer axial length tend to have higher FTD and more advanced FT grades.

Osteoarthritis & stroke: a bidirectional mendelian randomization study.

OBJECTIVE: The epidemiological evidence on the link between osteoarthritis (OA) and stroke remains inconclusive. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) study to determine the causality relationship between OA and stroke. DESIGN: Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. The data for OA at any site (n = 455,211), knee OA (n = 403,124), and hip OA (n = 393,873) were obtained from a meta-analysis of GWAS available in the UK Biobank and Arthritis Research UK Osteoarthritis Genetics resources. The MEGASTROKE consortium provided data for stroke (n = 446,696), ischemic stroke (IS) (n = 440,328) and its subtypes, and intracerebral hemorrhage (ICH) (n = 3,026). The main MR analysis was conducted by the inverse variance weighted (IVW) method. MR-Egger regression, MR pleiotropy residual sum and outlier, weighted median, Cochran Q statistic, and leave-one-out analysis approach were leveraged as supplements. RESULTS: We detected that higher risk of hip OA was significantly associated with overall stroke [IVW odds ratio (OR): 1.12, 95% confidence interval (CI): 1.06-1.20, P = 0.0002], IS (OR: 1.13, 95%CI: 1.06-1.21, P = 0.0003), and small vessel IS (OR: 1.25, 95%CI: 1.10-1.42, P = 0.0006). However, we found no evidence that stroke and subtypes had casual effects on OA in the reverse MR analyses. CONCLUSIONS: The present study provides genetic support that hip OA is a potential risk factor for overall stroke, IS, and small vessel IS. Further studies are warranted to elucidate the underlying mechanisms of causal associations between site-specific OA and stroke subtypes.

[Activation of cGAS/STING signaling pathway and its immunological role in the progression of nonalcoholic fatty liver disease].

Today, nonalcoholic fatty liver disease remains the most dominant chronic liver disease. Cyclic guanosine monophosphate-adenosine monosphosphate synthase (cGAS) is a cytosolic DNA sensor that catalyzes the synthesis of cyclic guanosine monophosphate, activates stimulator of interferon genes (STING), and releases type-I interferon cytokines to trigger immune responses. Exogenous or endogenous DNA acts as a cGAS ligand to activate the cGAS-STING signaling pathway, which plays a role in hepatitis, nonalcoholic fatty liver disease, liver cancer and other diseases, and affects liver disease progression and metabolism through mechanisms such as autophagy. This article reviews the activation of cGAS-STING pathway and its molecular immunological role in nonalcoholic fatty liver disease progression.

Nanoscale Electrostatic Modulation of Mega-Ampere Electron Current in Solid-Density Plasmas.

Transport of high-current relativistic electron beams in dense plasmas is of interest in many areas of research. However, so far the mechanism of such beam-plasma interaction is still not well understood due to the appearance of small time- and space-scale effects. Here we identify a new regime of electron beam transport in solid-density plasma, where kinetic effects that develop on small time and space scales play a dominant role. Our three-dimensional particle-in-cell simulations show that in this regime the electron beam can evolve into layered short microelectron bunches when collisions are relatively weak. The phenomenon is attributed to a secondary instability, on the space- and timescales of the electron skin depth (tens of nanometers) and few femtoseconds of strong electrostatic modulation of the microelectron current filaments formed by Weibel-like instability of the original electron beam. Analytical analysis on the amplitude, scale length, and excitation condition of the self-generated electrostatic fields is clearly validated by the simulations.

[Chronic toxicity of Multi-walled carbon nanotubes in human pleural mesothelial cells].

Objective: To explore the chronic toxicity and its potential mechanism of multi-walled carbon nanotube (MWCNT) in human pleural mesothelial cells. Methods: A sustainable exposure of MeT-5A cells to MWCNT at 10 µg/cm(2) for one year was conducted in 2016. During the exposure, the cell images and cell proliferation was recorded every 4 weeks. The cell apoptosis, cell cycle, cell migration and cell invasion were compared between the control cells and the cells after MWCNT exposure. Finally, the gene expression was screened with Affymetrix clariom D assay, and some of the significantly differential expressed genes was verified by RT-PCR. Results: Compared with the control group, the proliferation ability of the cells in the 1-year exposed group was significantly increased, and the rate of proliferation was about 2-3 times as that in the Control Group (F=481.32, P<0.05) . MeT-5A cells all showed cell cycle arrest effect, which showed the increase of G1 phase and the decrease of s phase and G2 phase (F=14.94, P<0.05) . The apoptosis rate of cells in the treated group was significantly higher than that in the control group after 6 months (F=15.12, P<0.05) , but the early apoptosis rate and the total apoptosis rate of cells in the treated group were not significantly different from those in the control group after 1 year (F=3.97, P<0.05) . The cell migration and invasion were both promoted by MWCNT. Furthermore, the differentially expressed genes was screened, to find 2, 878 genes with more than 2 folds changes. To further verified, RT-PCR was conducted with PIK3R3、WNT2B、VANGL2、ANXA1, and their expression changes were consistent with above. Conclusion: MWCNT might have a carcinogenic potential to MeT-5A cells after the long term exposure.

[Effect of PPAR-γ agonist pioglitazone on the prolifeiration of malignant nesothelionma cells induced by HMGB1].

Objective: To investigate the effect and mechanism of PPAR-γ agonist Pioglitazone (PGZ) on the proliferation of malignant mesothelioma (MM) cells. Methods: In December 2019, MM cell lines MSTO-211H and NCI-H2452 were incubated with different final concentrations of PGZ (0, 10, 50, 100, 150, and 200 µmol/L) for different periods of time (24 h, 48 h, and 72 h) , and then the cell proliferation level was detected by CCK8 assay. After given various final concentration of PGZ (0, 10, 50, 100, 150, 200 µmol/L) the for 72 hours, the changes of number and morphology of MM cells were observed under an inverted microscope. The expressions of PPAR-γ and HMGB1 mRNA were determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) after treatment of MM cells with PGZ of 0, 10, 50, 100 µmol/L for 72 h. The MM cells were treated with PGZ at concentration of 0, 100 µmol/L for 72 h, and the protein expressions of HMGB1 were examined using Western blotting and immunofluorescence; the protein expressions of Ki67 were assessed by immunohistochemistry. Results: The cell viability rate of MM cells was decreased after treated with PGZ (P<0.05) . Cell number in PGZ-treated group was significantly less than that in control group and morphology changes were observed under light microscope. QRT-PCR results revealed significantly increased PPAR-γ mRNA expression in the PGZ-treated group compared to the control group (P<0.05) . There was a significant decrease in the mRNA expression level of HMGB1 in the PGZ-treated group (100 µmol/L) as compared to the control group in MSTO-211H (P<0.05) ; however, the expression level of HMGB1 in NCI-H2452 was an increase or no significant differences (P>0.05) . Western blotting and immunofluorescence results showed that the protein expression of HMGB1 was reduced in the PGZ-treated group compared with the control group in MSTO-211H (P<0.05) , but the protein expression of that in NCI-H2452 was no significant differences (P>0.05) . Immunohistochemistry results showed increased expression of proliferation marker Ki-67. Conclusion: Pioglitazone suppresses the proliferation of MM cells through inhibition of HMGB1 by the activation of PPAR-γ.

[microRNA-30d can inhibit the proliferation, migration and invasion of human mesothelial cell MSTO-211H].

Objective: To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H. Methods: In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method. Results: After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group (P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) (P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 µm(2) and 58.19±1.82 µm(2)) were significantly lower than MSTO-211H+miR NC cells group (54.42±5.26 µm(2) and 88.32±1.96 µm(2)) (P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group (P<0.01) . Conclusion: miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.

[Study on malignant transformation of MeT-5A cells induced by chrysotile].

Objective: To study the cytotoxicity and malignant transformation ability of chrysotile on MeT-5A cells. Methods: In June 2016, lactate dehydrogenase (LDH) method was used to detect the cytotoxicity of chrysotile to MeT-5A cells. MeT-5A cells were treated with 5 µg/cm(2) chrysotile intermittently for 24 h a time, once a week and a total of 28 times. After the cells showed anchorage independent growth, the cell features of malignant transformation were identified by colony forming frequency in soft agar, and the soft agar colony formation rates were calculated. The activities of key speed limiting enzymes of glycolysis metabolism including hexokinase (HK) , phosphofructokinase (PFK) and pyruvate kinase (PK) were determined by UV colorimetry. Results: Chrysotile was cytotoxic to MeT-5A cells in a concentration-dependent decline. Compared with the control group, the relative survival rates of MeT-5A cells were significantly decreased after exposed to chrysotile at 10, 20, 40 and 80 µg/cm(2) (P<0.05) . After 28 times of exposure, the growth rate of the cells in chrysotile transformed MeT-5A cells was accelerated, the arrangement was disordered, the contact inhibition was lost, and the double layer growth appeared, which could grow on soft agar. The colony forming rate of the chrysotile transformed MeT-5A cells was 18.33‰±2.49‰. Compared with the control group (0) , the difference was statistically significant (P<0.01) . The activities of glycolysis related kinase including PK [ (19.51±1.52) U/L], PFK[ (0.12±0.02) U/10(4) cell] and HK[ (0.26±0.01) U/10(4) cell] were increased in the chrysotile transformed MeT-5A cells compared with control group [ (25.00±1.04) U/L、(0.15±0.01) U/10(4) cell and (0.33±0.01) U/10(4) cell] (P<0.01) . Conclusion: Chrysotile can induce malignant transformation of MeT-5A cells and increase the activities of glycolysis related kinases including PK, PFK and HK.

[Analysis of influencing factors of textile workers' occupational stress].

Objective: To explore the occupational stress status and influencing factors of workers in a textile factory in Zhejiang Provice. Methods: In October 2018, 505 workers from a textile factory in Zhejiang Province were selected as research objects by convenient sampling method. A total of 505 questionnaires were distributed, 495 of which were effective and the effective recovery rate was 98.0%. Job Content Questionnaire (JCQ) and Effort Reward Imbalance Questionnaire (REI) were used to investigate textile workers' occupational stress and analyze its influencing factors. The differences of the composition ratio of different groups were tested by χ(2) test. The influencing factors such as age, gender and occupation on occupational stress were analyzed by multivariate logistic regression. Results: ERI analysis results showed that the high and low occupational stress accounted for 30.1% and 69.9%, respectively. The differences of occupational stress among workers of different job types and working ages were statistically significant (P<0.05) . The detection rates of high occupational stress of paper workers and spinners were 47.8% (11/23) and 44.8% (30/67) , respectively, higher than other jobs. The detection rate of high occupational stress for workers with more than 5 years of service was 46.4% (13/28) . The results of JCQ analysis showed that there was no statistical significance in the differences of daily working hours and length of service between different gender, education levels, types of work patterns, and occupational stress (P>0.05) . Job types had significant effects on the occupational stress defined by ERI (P<0.05) , the risk of occupational stress was 2.151 times than that of the coiler. Conclusion: There are significant differences in occupational stress risk among workers of different types of work in textile industry, so different measures should be taken to prevent and control occupational stress in different jobs.

Role of epigenetic mechanisms in transmitting the effects of neonatal sevoflurane exposure to the next generation of male, but not female, rats.

BACKGROUND: Clinical studies report learning disabilities and attention-deficit/hyperactivity disorders in those exposed to general anaesthesia early in life. Rats, primarily males, exposed to GABAergic anaesthetics as neonates exhibit behavioural abnormalities, exacerbated responses to stress, and reduced expression of hypothalamic K+-2Cl- Cl- exporter (Kcc2). The latter is implicated in development of psychiatric disorders, including male predominant autism spectrum disorders. We tested whether parental early life exposure to sevoflurane, the most frequently used anaesthetic in paediatrics, affects the next generation of unexposed rats. METHODS: Offspring (F1) of unexposed or exposed to sevoflurane on postnatal day 5 Sprague-Dawley rats (F0) were subjected to behavioural and brain gene expression evaluations. RESULTS: Male, but not female, progeny of sevoflurane-exposed parents exhibited abnormalities in behavioural testing and Kcc2 expression. Male F1 rats of both exposed parents exhibited impaired spatial memory and expression of hippocampal and hypothalamic Kcc2. Offspring of only exposed sires had abnormalities in elevated plus maze and prepulse inhibition of startle, but normal spatial memory and impaired expression of hypothalamic, but not hippocampal, Kcc2. In contrast to exposed F0, their progeny exhibited normal corticosterone responses to stress. Bisulphite sequencing revealed increased CpG site methylation in the Kcc2 promoter in F0 sperm and F1 male hippocampus and hypothalamus that was in concordance with the changes in Kcc2 expression in specific F1 groups. CONCLUSIONS: Neonatal exposure to sevoflurane can affect the next generation of males through epigenetic modification of Kcc2 expression, while F1 females are at diminished risk.

[Features and influencing factors of self-discrimination among HIV/AIDS patients according to sex].

Objective: To investigate the features and influencing factors of self-discrimination among patients with HIV/AIDS according to sex. Methods: A total of 2 432 HIV/AIDS patients were recruited in Yunnan, Henan, Hubei, Jiangsu, Shanxi, Jilin, and Inner Mongolia provinces by a multistage stratified cluster sampling method, based on HIV epidemic and transmission modes, from May 2013 to October 2013. All participants were ≥18 years old, and we excluded those with mental disorders, hearing loss or other factors that prevented them from properly answering questions, and those who were unwilling to participate. A self-designed questionnaire was conducted to collect information about self-discrimination features and social behavior changes among HIV/AIDS patients. Differences in performance and self-discrimination features between participants of different sexes were compared using the chi-squared test. Factors influencing self-discrimination were analyzed by sex, using unconditional logistic regression. Results: Of the 2 432 cases, 78.9%(1 918 cases)were male and 21.1%(514 cases)female. The proportion of self-discrimination overall was 76.1%(1 850 cases); this proportion among female HIV/AIDS patients was 80.5%(414 cases), which was higher than that among men(74.9%, 1 436 cases)(χ2=7.17, P=0.007). Of the 11 forms of self-discrimination performance, proportions of feeling guilt, shame, and self-abasement among participants were greater than 50%. Proportions of feeling shame, inferiority, and blaming others among females were 61.3%, 59.5%, and 45.3%, respectively, which were higher than these among males(49.8%, 50.0%, 28.4%, respectively)(P<0.01). Multivariate unconditional logistic regression analysis showed that the risk of self-discrimination among those with HIV confirmatory testing time ≥1 year was higher than those with HIV confirmatory testing time <1 year(females: OR=35.67, 95%CI:17.28-73.64; males: OR=8.74, 95% CI:6.79-11.25). Compared with other occupations, the risk of self-discrimination among male farm workers was higher(OR=1.62, 95% CI:1.03-2.54). The risks of self-discrimination in males who had been infected with HIV by transmission routes of blood transfusion or blood collection(OR=2.38, 95% CI:1.31-4.30), injection drug use(OR=1.78, 95% CI:1.09-2.91), and male-to-male sexual behavior(OR=1.48, 95%CI:1.08-2.03)were higher than in males infected via heterosexual behavior. Conclusion: Female HIV/AIDS patients are more likely to engage in self-discrimination than male patients. Self-discrimination mainly takes the form of feeling remorse, shame, and inferiority. Confirmatory testing time ≥1 year, occupation as a farm work, and routes of transmission via blood transfusion or collection, injection drug use, and male-to-male sexual behavior are influencing factors of self-discrimination among male HIV/AIDS patients. Confirmatory testing time ≥1 year is the influencing factor of self-discrimination among female HIV/AIDS patients.

[Quality of life and its related factors among HIV/AIDS patients from HIV serodiscordant couples in Zhoukou of Henan province].

OBJECTIVE: To investigate the quality of life and its related factors among HIV/AIDS patients from HIV serodiscordant couples in Zhoukou city of Henan province. METHODS: During January to May in 2015, by the convenience sample, World Health Organization Quality of Life Questionnaire for Brief Version (WHOQOL-BREF) (Chinese version) and a self-edited questionnaire were used to investigate 1 251 HIV/AIDS patients who were confirmed with HIV positive by local CDC, registered in"HIV serodiscordant family" and agreed to participate in a face-to-face interview with above 18 year-old based on the local CDC , township hospitals and village clinics of 9 counties and 1 district of Zhoukou city, excluding the HIV/AIDS patients who were in divorce, death by one side, unknowing about his HIV status, with mental illness and disturbance of consciousness, incorrectly understanding the content of the questionnaire, and reluctant to participate in this study. The scores of quality of life of physical, psychological, social relations, and environmental domain were calculated. The related factors of the scores of different domains were analyzed by Multiple Two Classification Unconditioned Logistic Regression. RESULTS: The scores of investigation objects in the physical, psychological, social relations, and environmental domain were 12.00± 2.02, 12.07 ± 2.07, 11.87 ± 1.99, and 11.09 ± 1.84, respectively. The multiple Unconditioned Logistic Regression analysis indicated that age <40 years, on ART and no other sickness in last two weeks were beneficial factors associated with physical domain with OR (95%CI): 0.61 (0.35-1.06), 0.52 (0.30-0.90), and 1.66 (1.09-2.52), respectively. The possibility of no poverty and no other sickness in last two weeks increased to 0.15(0.09-0.26) and 1.57(1.06-2.33) times of those who was in poverty and with other sickness in last two weeks in physical domain. The possibility of participants who were below 40 years old and with children increased to 0.58 (0.34-0.98) and 0.37 (0.23-0.57) times of who were above 40 years old and without children in psychological domain. The factors of with AIDS related symptoms, no children and with other sickness in last two week were found to be significantly associated with environmental domain with OR (95%CI): 0.65 (0.48-0.88), 0.66 (0.51-0.85), and 0.65 (0.51-0.84), respectively . CONCLUSION: The scores of every domain of quality of life in HIV serodiscordant couples of Zhoukou city were good. Age, whether having AIDS related symptoms, whether to accept ART , children, status of poverty, and whether suffering from other diseases in last two weeks were the main factors associated with the quality of life.

[Efficacy of Kolofort for the treatment of patients with irritable bowel syndrome]. / Effektivnost' Koloforta v lechenii bol'nykh s sindromom razdrazhennogo kishechnika.

AIM: to determine the efficacy and safety of Kolofort in the treatment of patients with irritable bowel syndrome (IBS). SUBJECTS AND METHODS: 52 patients (16 men and 36 women) aged 26 to 59 years were examined over 4 months to rule out organic disease. The diagnosis of IBS was established on the basis of the Rome III diagnostic criteria (2006). Seven patients were diagnosed as having IBS with a preponderance of constipation; 3 had IBS with a preponderance of diarrhea, and 42 had mixed IBS. Thereafter they were given Kolofort, a combination release-active antibody drug having anxiolytic, anti-inflammatory, and spasmolytic effects. Kolofort affects the ligand-receptor interactions of the brain-specific protein S-100 with serotonin receptors and σ1-receptors in the central nervous system and that of histamine with histamine H4 receptors in the gastrointestinal tract and modifies (regulates) the functional activity of tumor necrosis factor-α (TNF-α). The regulatory action of the drug at the level of the central and autonomic nervous system and the immune system manifests itself as spasmolytic, anti-inflammatory, and sedative effects, which as a whole effectively normalizes gastrointestinal motility. For 3 months, the patients took sublingual Kolofort in a dose of 2 tablets thrice daily for 2 weeks, then 2 tablets twice daily for 2.5 months. Control was made 2 weeks, 1, 2, and 3 months after treatment initiation. The investigators assessed abdominal pain syndrome, defecation disorders, abdominal distension, and flatulence by the visual analogue scale (VAS-IBS questionnaire), visceral sensitivity index (VSI questionnaire), quality of life (QL) in patients with IBS (IBS-QoL questionnaire), and stool form according to the Bristol Stool Chart and measured the levels of TNF-α and interleukin (IL)-1ß and IL-10 before and after treatment. RESULTS: The efficacy of Kolofort showed itself within 2 weeks of its administration against all the study functional parameters (pain, defecation disorder, and flatulence). After one month of therapy, the efficacy of Kolofort achieved meaningful statistical significance against abdominal pain, complaints of flatulence, visceral sensitivity index, and QL. The statistically significant restoration of a stool form was achieved 2 months after treatment and 3-month Kolofort treatment showed a clear-cut positive clinical effect that appeared as reductions in pain syndrome (214±0.22; р < 0.001) and visceral hypersensitivity symptoms (from 30.33±2.9 to 67.76±6.5; р < 0.001), improvements in subjective sensations associated with defecation disorders (from 6.95±0.71 to 2.74±0.28; р < 0.001), stool form, and QL indicators (from 103.48±9.06 to 44.95±5.4; р < 0.001), and a decrease in blood TNF-α levels after treatment termination (from 9.16 to 7.02 pg/ml; р < 0.026). A Kolofort treatment cycle for IBS produced no clinically relevant side effects. CONCLUSION: Kolofort was highly effective in relieving symptoms, in normalizing the psychological status, and in lowering the levels of TNF-α in the treatment of IBS. The efficacy of the drug was achieved because of its combined effect on the main components of the pathogenesis of IBS.

[Changes of microRNAs profiling in mesothelial cells exposed to multi-walled carbon nanotubes].

Objective: To explore the cytotoxicities of MWCNT to the mesothelial cells and screen the changes of microRNA profile after exposure to MWCNT. Methods: A LDH method was used to test the cytotoxicities of MWCNT to MeT-5A cell lines. And then the differentially expressed miRNAs between mesothelioma cells and normal mesothelial cells were selected from previous work of research group. Among the significant expression changed miRNAs, 5 were verified by RT-qPCR in mesothelioma cells. The same five ones were further tested in MeT-5A cells exposed to 10 µg/cm2 MWCNT for 8, 24, 48, 72 h by RT-qPCR. Target genes of 5 miRNAs were predicted using Targetscan and miRanda softwares. David6.7 was used to perform GO enrichment and KEGG pathway analysis of target genes. All the data were analyzed by one-way ANOVA and Dunnett-T test in SPSS17.0. Results: After 24 h exposure to MWCNT, cell proliferation was significantly suppressed at more than 20 µg/cm2 concentration. Among the differentially expressed miRNAs, 5 were chosen to further vestified, namely hsa-miR-155 (up-regulated) , hsa-miR-30 d-5p, hsa-miR-34c-5p, hsa-miR-28-5p and hsa-miR-324-5p (down-regulated) , which were consistent with the miRNA array results. The 5 miRNAs also had the same expression changes in MeT-5A cells after exposure to 10 µg/cm2 MWCNT for different time periods. The potential target genes of the 5 miRNAs may be AKAP13, CCND3, Twist and E-Cadherin, which mainly involved in TGF-ß signal pathway, small cell lung cancer, etc. Conclusion: MWCNT could induce to MeT-5A cells, and also cause miRNA expression changes. The differential changed miRNAs may involve in cancer related signal pathways.

Molecular cloning and characterization of a proliferating cell nuclear antigen gene by chemically induced male sterility in wheat (Triticum aestivum L.).

Although a number of studies have shown that chemical hybridizing agents (CHAs) affect anther growth and regulate cell-cycle progression, little is known about the molecular and cellular mechanisms involved. Proliferating cell nuclear antigen (PCNA) is an essential factor in DNA replication, and in many other processes in eukaryotic cells. In this study, the open reading frame of TaPCNA, the PCNA in wheat (Triticum aestivum L.), was cloned by reverse transcription polymerase chain reaction (RT-PCR). Sequence analysis revealed that this gene was 792-bp long and encoded a protein with 234 amino acids. Alignment of the TaPCNA-predicted sequence revealed a high degree of identity with PCNAs from other plant species. A subcellular localization assay indicated that TaPCNA was localized in the nucleus. The TaPCNA was cloned into the prokaryotic expression plasmid pET32a, and the recombinant plasmid was transformed into BL21 (DE3). TaPCNA expression was induced by 0.5 mM isopropyl-beta-D-thiogalactopyranoside and verified using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot assays, which indicated that the fusion protein was successfully expressed. The gene involved in the G1-to-S transition, Histone H4, was downregulated by 1376- CIMS, which is a chemically induced male sterility line. However, a semi-quantitative RT-PCR revealed that TaPCNA expression was upregulated in 1376-CIMS. Our results suggest that CHAs (SQ-1) induce DNA damage in wheat anthers. DNA damage results in either the delay or arrest of cell-cycle progression, which affects anther development. This study will help to elucidate the mechanisms of SQ-1-induced male sterility.

Controlling graphene ultrafast hot carrier response from metal-like to semiconductor-like by electrostatic gating.

We investigate the ultrafast terahertz response of electrostatically gated graphene upon optical excitation. We observe that the photoinduced terahertz absorption increases in charge neutral graphene but decreases in highly doped graphene. We show that this transition from semiconductor-like to metal-like response is unique for zero bandgap materials such as graphene. In charge neutral graphene photoexcited hot carriers effectively increase electron and hole densities and increase the conductivity. In highly doped graphene, however, photoexcitation does not change net conducting carrier concentration. Instead, it mainly increases electron scattering rate and reduce the conductivity.

[APPLICATION OF DIFERELIN AND ITS PERSPECTIVES].

The article presents a brief overview of luteinizing hormone-releasing hormone analogs in the treatment of prostate cancer. The authors report their experience with this drug class by an example of Diferelin. The experience with abiraterone in treatment of patients with hormonal resistance is described.

[PATHOLOGICAL CHANGES IN THE KIDNEYS IN POLYTRAUMA FATALITIES].

This paper presents a morphological study of kidneys of 30 patients, who died as a result of multiple injuries. In 96.7% of decedents, in the absence of external signs of kidney integrity violation, there were plasmorrhagia, hemorrhage, destruction of glomeruli and tubules, epithelium desquamation, emergence of hyaline casts in the tubules. After 3 days lymphoid leukocyte infiltration in the parenchyma of the kidney was found, and after 30 days collagen fibers around the glomeruli and tubules were detected, which is representative of renal fibrosis.