Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Performance of the ATRIA Bleeding Score in Predicting the Risk of In-Hospital Bleeding in Patients with ST-Elevation or Non-ST-Elevation Myocardial Infarction

ABSTRACT Introduction: A clear assessment of the bleeding risk score in patients presenting with myocardial infarction (MI) is crucial because of its impact on prognosis. The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA score is a validated risk score to predict bleeding risk in atrial fibrillation (AF), but its predictive value in predicting bleeding after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) patients receiving antithrombotic therapy is unknown. Our aim was to investigate the predictive performance of the ATRIA bleeding score in STEMI and NSTEMI patients in comparison to the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) and ACUITY-HORIZONS (Acute Catheterization and Urgent Intervention Triage strategY-Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) bleeding scores. Methods: A total of 830 consecutive STEMI and NSTEMI patients who underwent PCI were evaluated retrospectively. The ATRIA, CRUSADE, and ACUITY-HORIZONS risk scores of the patients were calculated. Discrimination of the three risk models was evaluated using C-statistics. Results: Major bleeding occurred in 52 (6.3%) of 830 patients during hospitalization. Bleeding scores were significantly higher in the bleeding patients than in non-bleeding patients (all P<0.001). The discriminatory ability of the ATRIA, CRUSADE, and ACUITY-HORIZONS bleeding scores for bleeding events was similar (C-statistics 0.810, 0.832, and 0.909, respectively). The good predictive value of all three scores for predicting the risk of bleeding was observed in NSTEMI and STEMI patients as well (C-statistics: 0.820, 0.793, and 0.921 and 0.809, 0.854, and 0.905, respectively). Conclusion: This study demonstrated that the ATRIA bleeding score is a useful risk score for predicting major in-hospital bleeding in MI patients. This good predictive value was also present in STEMI and NSTEMI patient subgroups.

Effect of SR9009 on myocardial injury in endotoxemic mice / 中华麻醉学杂志

Objective:To evaluate the effect of SR9009 on myocardial injury in endotoxemic mice.Methods:Eighteen SPF healthy male C57BL/6 mice, aged 5 weeks, weighing 21-24 g, were divided into 3 groups ( n=6 each) by the random number table method: control group (C group), endotoxemia group (lipopolysaccharide [LPS] group) and endotoxemia + SR9009 group (LPS+ SR group). SR9009 50 mg/kg was intraperitoneally injected at 4: 00 p. m. in LPS+ SR group. The endotoxemic model was prepared by intraperitoneal injection of LPS 15 mg/kg at 10 a. m. on the second day in mice. The left ventricular function was monitored by echocardiography at 9 h after LPS injection. Blood samples were collected from the heart cavity under direct visualization for determination of the serum creatine kinase isoenzymes (CK-MB), lactic dehydrogenase (LDH) and cardiac troponin I (cTnI) levels by enzyme-linked immunosorbent assay. Myocardial tissues were obtained and stained with HE for microscopic examination of the pathological changes (with a light microscope) and for determination of the expression of Beclin1, P62 and microtubule-associated protein 1 light cain 3 (LC3) (by Western blot), and the ratio of LC3Ⅱ to LC3Ⅰ was calculated. Results:Compared with group C, the ejection fraction and short-axis fractional shortening were significantly decreased, the left ventricular end-diastolic internal diameter and left ventricular end-systolic internal diameter were shortened, the left ventricular end-diastolic posterior wall thickness and left ventricular end-systolic posterior wall thickness were decreased, serum CK-MB, LDH and cTnI levels were increased, P62 expression in myocardial tissues was down-regulated, Beclin1 expression was up-regulated, LC3Ⅱ/LC3Ⅰ ratio was increased ( P<0.05), and the pathological changes were found in myocardial tissues in group LPS. Compared with group LPS, the ejection fraction and short-axis fractional shortening were significantly increased, the left ventricular end-systolic internal diameter was shortened, and the left ventricular end-diastolic posterior wall thickness was decreased ( P<0.05), no significant change was found the left ventricular end-diastolic internal diameter and left ventricular posterior end-systolic wall thickness ( P>0.05), the serum CK-MB, LDH and cTnI levels were decreased, and P62 expression in myocardial tissues was up-regulated, Beclin1 expression was down-regulated, LC3Ⅱ/LC3Ⅰ ratio was decreased ( P<0.05), and the pathological changes in myocardial tissues were significantly attenuated in LPS+ SR group. Conclusions:SR9009 can alleviate myocardial injury in endotoxemic mice, and the mechanism may be related to inhibition of autophagy.

Investigation on 90Sr and 137Cs activity concentrations in water in Hangzhou urban area from 2012 to 2020 / 中华放射医学与防护杂志

Objective:To investigate the activity concentrations of 90Sr and 137Cs in water in Hangzhou urban area. Methods:From 2012 to 2020, Qiantang River water as an important drinking water source, tap water as direct drinking water for residents, and West Lake water in tourists crowded area were selected forwater quality monitoring with respect to conctnts of 90Sr and 137Cs. The activity concentrations of 90Sr and 137Cs in water samples, as collected in wet and dry seasons resepectively, were determined by radiochemical analysis, with the 137Cs to 90Sr activity ratios obtained. Results:From 2012 to 2020, the activity concentrations of 90Sr and 137Cs in tap water were (2.0±1.1) - (7.4±0.4) mBq/L and (0.45±0.06) - (7.1±0.6) mBq/L, respectively. The 137Cs to 90Sr activity ratios ranged from 0.07 to 2.40. The activity concentrations of 90Sr and 137Cs in Qiantang River were (3.7±1.1) - (17.0±4.4) mBq/L and (0.28±0.01) - (15.0±4.5) mBq/L, respectively. The 137Cs to 90Sr activity ratios ranged from 0.03 to 0.90. The activity concentrations of 90Sr and 137Cs in West Lake water were (2.2±0.5) - (11.0±2.0) mBq/L and (0.32±0.04) - (7.9±1.9) mBq/L, respectively. The 137Cs to 90Sr activity ratios ranged from 0.05 to 1.20. Conclusions:The activity concentrations of 90Sr and 137Cs in water in Hangzhou urban area were at the background levels, lower than the concentration limits, 10 Bq/L both for 90Sr and 137Cs recommended by WHO in the 4 th edition of Guidelines for Drinking Water Quality.

CircRNA-SCAF8 promotes vascular endothelial cell pyroptosis by regulating the miR-93-5p/TXNIP axis / 浙江大学学报·医学版

OBJECTIVES@#To investigate the role and mechanism of circRNA-SR-related CTD associated factor 8 (SCAF8) in regulating endothelial cell pyroptosis in high glucose environment.@*METHODS@#Human umbilical vein endothelial cells (HUVECs) were cultured and divided into six groups. The normal control group and high glucose control group were cultured in cell culture medium with 5 and 33 mmol/L glucose, respectively. The RNA control group, circRNA-SCAF8 inhibition group, miR-93-5p overexpression group and miR-93-5p inhibition group were added with non-functional siRNA, circRNA-SCAF8 inhibitor, miR-93-5p overexpression molecule and miR-93-5p inhibitor in high glucose environment, respectively. Cell viability and pyroptosis were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and Hoechst 33342/propidium iodide fluorescence double staining. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of pyroptosis-related factors including apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartic acid specific protease-1 (caspase-1) and Gasdermin D (GSDMD), NOD like receptor protein 3 (NLRP-3), thioredoxin interacting proteins (TXNIP), IL-18 and IL-1β. The expression of circRNA-SCAF8, miR-93-5p and TXNIP was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to locate circRNA-SCAF8 and miR-93-5p. Dual luciferase assay was used to verify the targeted regulatory relationship between miR-93-5p and upstream and downstream molecules.@*RESULTS@#Compared with the RNA control group, the cell survival rate of circRNA-SCAF8 inhibition group and miR-93-5p overexpression group increased (both P<0.01), the pyroptosis decreased (both P<0.01), and the expressions of pyroptosis-related factors such as TXNIP, NLRP-3, caspase-1, GSDMD, ASC, IL-18 and IL-1β were significantly decreased (all P<0.05). The expression of miR-93-5p was significantly increased after inhibition of circRNA-SCAF8 (P<0.01), and the expression of circRNA-SCAF8 tended to decrease after overexpression of miR-93-5p, but with no statistical significance (P>0.05). Dual luciferase assay showed that miR-93-5p downre-gulated circRNA-SCAF8 expression by binding to the 3 ´ UTR region of circRNA-SCAF8, and miR-93-5p downregulated TXNIP expression by binding to the 3 ´ UTR region of TXNIP. FISH showed that circRNA-SCAF8 and miR-93-5p were both located in the cytoplasm and were highly associated in the cells. qRT-PCR showed that the relative expression of TXNIP increased or decreased after overexpression or inhibition of miR-93-5p compared with the RNA control group, respectively (both P<0.05), suggesting that miR-93-5p could regulate TXNIP gene expression.@*CONCLUSIONS@#CircRNA-SCAF8/miR-93-5p/TXNIP axis is involved in the regulation of pyroptosis in HUVECs under high glucose.

Effect of circadian rhythm changes on the expression of RORs and the RORs agonist SR1078 on corneal epithelial wound repair / 中华实验眼科杂志

Objective:To investigate the effect of circadian rhythm changes on the expression of retinoic acid-related orphan receptors (RORs) and the RORs agonist SR1078 on corneal epithelial wound repair.Methods:A total of 228 SPF C57BL/6 female mice aged 6-8 weeks old were selected, and 180 mice were divided into the normal circadian rhythm group, full-day group, full-night group, 12-hour reversed circadian rhythm group and 3-week reversed circadian rhythm group, with 36 mice in each group.The remaining 48 mice were randomly divided into phosphate buffered saline (PBS) control group and SR1078 group by random number table method, with 24 mice in each group.According to grouping, the mice were placed in a light box where the light (light intensity of 300 lx) and dark time could be controlled.The light time of the normal circadian rhythm group, the PBS control group and the SR1078 group in the light box was from 7: 00 to 19: 00, and the dark time was from 19: 00 to 7: 00 the next day.According to the Zeitgeber Time method, the starting time of light at 7: 00 was recorded as ZT0, and the time of closing light at 19: 00 was recorded as ZT12.Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of RORα and RORγ mRNA at ZT1, ZT5, ZT9, ZT13, ZT17, ZT21 in the five groups.In the PBS control group and SR1078 group, a golf-like knife was used to establish the mouse corneal epithelial injury model, and the model eyes were administered with drugs once every 6 hours according to the grouping.The corneal epithelial defect area was measured with Adobe Photoshop CC2019 software, and the corneal epithelial defect rate was calculated and compared between the two groups.The correlation between the relative expression levels of RORα and RORγ mRNA in mice corneal epithelium of the five groups and corneal epithelial defect rate in the PBS control group and SR1078 group was analyzed.The corneal epithelium repair was observed by whole cornea spreading and immunofluorescence staining, and the number of corneal epithelial dividing cells in the PBS control group and the SR1078 group was calculated and compared.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Laboratory Animal Ethics Committee of Jinan University (No.JN-A-2002-01).Results:Compared with the normal circadian rhythm group, the relative expression levels of RORα/RORγ mRNA in the full-day group, full-night group, 12-hour reversed cirdian rhythym group and 3-week reversed cirdian rhythym group showed an overall decreasing trend.There was a statistically significant difference in the corneal epithelial defect rate between the PBS control group and the SR1078 group at different time points after modeling ( Fgroup=74.01, P<0.001; Ftime=5 171.48, P<0.001). Twelve hours after modeling, the corneal epithelial defect rate in the SR1078 group was significantly lower than that in the PBS control group, and the difference was statistically significant ( P<0.05). The relative expression levels of RORα and RORγ mRNA in corneal tissue was moderately positively correlated with the corneal epithelial defect rate in mice ( r=0.614, 0.537; both at P<0.01); The regression equation of the straight line between the relative expression level of RORα mRNA and the change in corneal epithelial defect rate was Y=33.153X-43.052 ( F=20.58, P<0.001), and the linear regression equation between the relative expression level of RORγ mRNA and the change of corneal epithelial defect rate was Y=2.764X-1.364 ( F=13.11, P<0.001). There was a significant overall difference in the number of corneal epithelial dividing cells at various time points following modeling between the PBS control group and the SR1078 group ( Fgroup=160.55, P<0.001; Ftime=83.57, P<0.001). The number of dividing cells in the SR1078 group was significantly less than that in the PBS control group at 24, 30, and 36 hours following modeling, and the differences were statistically significant (all at P<0.05). Conclusions:Circadian rhythm changes reduce the expression of RORα and RORγ mRNA in the mouse cornea.SR1078 can promote the expression of RORα and RORγ mRNA in corneal epithelium to decrease the number of mouse corneal epithelial dividing cells, and inhibit the repair after corneal trauma.

The investigation on the radioactivity level of 90Sr in tea leaves in the vicinity of Ningde nuclear power plant / 中国辐射卫生

Objective To investigation the radioactivity level of 90Sr in tea leaves within and outside 30 km range of Ningde nuclear power plant. Methods The tea leaves within and outside the 30 km range of Ningde Nuclear Power Plant were collected from 2013 to 2018. According to“Radiochemical analysis of strontium-90 in water and ash of biological samples” (HJ 815—2016), the separation and analysis of 90Sr-90Y were carried outusing the method of di (2-ethylhexyl) phosphate (HDEHP) chromatography. Results During the period of 2013-2018, the radioactivity concentrations of 90Sr in the tea leaves within the range of 30 km around the Ningde nuclear power plant were 0.486～13.29 Bq/kg and that of 90Sr in the tea leaves outside the range of 30 km around the nuclear power station were 1.021～17.19 Bq/kg. Conclusion During the six years of operation in Ningde Nuclear Power Plant, there was no increase in the radioactivity level of 90Sr in the tea leaves around the nuclear power plant.

Observation on the effect of 90Sr-90Y application combined with corn paste in the treatment of corns / 中国辐射卫生

Objective To evaluate the clinical efficacy and satety of 90Sr-90Y application combined with corn paste in the treatment of corns. Methods 85 patients with corns in the First People's Hospital of Tianmen from September 2019 to December 2020 were selected and randomly divided into group A, group B and group C based on random number table. In group A, 28 cases were treated with simple 90Sr-90Y application; in group B, 27 cases were treated with 90Sr-90Y application plus intermittent corns paste; in group C, 30 cases were treated with 90Sr-90Y application plus continuous corns paste.The treatment effect, recovery time, recurrence rate and incidence of adverse reactions of the three groups were compared. Results The cure rates of the three groups were 78.57% (21/28), 81.48% (22/27) and 83.33% (25/30), with no significant difference (P > 0.05); the total effective rates were 92.86% (26/28), 92.59% (25/27) and 96.67% (29/30), the difference was not significant (P > 0.05); the cure time was (5.67 ± 1.80) weeks, (2.82 ± 1.11) weeks and (2.24 ± 1.05) weeks, the cure time of the B and C groups was significantly shorter than that of the A group (P < 0.05); The incidence of adverse reactions were 9.52% (2/21), 4.55% (1/22) and 4.00% (1/25), respectively, the difference was not significant (P > 0.05); the incidence of adverse reactions were 3.57% (1/28), 11.11% (3/27) and 26.67% (8/30), the incidence of adverse reactions in group C was higher than Group A (P < 0.05). Conclusion The combination of 90Sr-90Y application and intermittent corns paste in the treatment of corns has good curative effect, low recurrence rate, short cure time and few adverse reactions. It is worthy of clinical promotion.

Application of 210Bi removal by anion exchange resin in 90Sr analysis / 中华放射医学与防护杂志

Objective:To overcome the disadvantages of bismuth removal by bismuth sulfide precipitation method recommended by existing analytical standards and improve the quality of analytical result.Methods:Based on 201×7 anion exchange resin, the experimental process of bismuth removal was designed, and verified by using spiked samples and IAEA test samples.Results:Bismuth was removed by anion exchange resin. In the removal experiments of strontium, yttrium and bismuth, the chemical recovery rate of strontium and yttrium could reach (98.6 ± 0.8)% and (98.5 ± 0.7)%, respectively, with no Bi 2S 3 precipitation found. The relative standard deviation between analytical result and theoretical values was -2.97% to 5.94%, better than 3.96%-17.8% by the standard bismuth removal method. Through validation using IAEA test samples, the relative standard deviation between the reported value and the target value for 90Sr was between 3.40%-7.09%, and all the results were acceptable. Conclusions:Bismuth could be quantitatively removed using anion exchange resin without adsorption of strontium and yttrium. In addition, the bismuth removal solution system of anion exchange resin was the same as the elution system in 90Sr analysis, and the purpose of rapid bismuth removal could be achieved without conversion system. Compared with the current standard analytical method, it was feasible and better to quantitatively remove bismuth based on anion exchange resin, which could meet the needs of routine analysis of 90Sr.

Investigation on 90Sr level in offshore seawater and seafood therein around Sanmen nuclear power plant site and assessment of committed effective dose from 2015 to 2019 / 中华放射医学与防护杂志

Objective:To investigate and analyze the radioactivity level of 90Sr in offshore seawater and seafood therein around Sanmen nuclear power plant (NPP) and to estimate the annual committed effective dose to local population from ingestion of 90Sr in seafood from 2015 to 2019. Methods:From 2015 to 2019, the offshore seawater and 3 kinds of marine products grown locally in Sanmen and consumed by local residents were collected for measurement of the level of 90Sr radioactivity. The committed effective doses to the local population were estimated based on monitoring result and consumption data on seafood in Zhejiang offshore. Results:The radioactivity concentrations of 90Sr ranged from 2.4 to 4.1 mBq/L in the seawater, close to the natural radioacrive background level and from 6.7×10 -2 to 1.3 Bq/kg in seafood, lower than the standard values specified in the "Limited concentrations of radioactive materials in foods" (GB 14882-94). Annual committed effective dose to the local population from 90Sr attributable to consumption of seafood in Sanmen County from 2015 to 2019 were 2.2×10 -4-4.2×10 -4mSv, respectively, far lower than the worldwide committed effective dose result ing from internal exposure. Conclusions:From 2015 to 2019, the radioactivity concentration of 90Sr in seawater and seafood are stable, with neglectable dose burden to the local population.

SR1001 Inhibits Clostridium difficile Infection by Interfering Phosphorylation of PI3K/AKT/mTOR Pathway / 胃肠病学

Background: Clostridium difficile infection (CDI) is the most commonly seen opportunistic infection. Although antibiotic therapy is the first-line treatment, there are still some problems existed such as poor therapeutic effect, recurrence of infection and recrudescence. Therefore, it is necessary to develop new anti-infectious drugs. Aims: To explore the possible intervention effect of SR1001 on CDI and its potential mechanism, and to explore its potential intervention targets. Methods: Clostridium difficile (C. difficile) was cultured with HT-29 cells, and were divided into control group, CDI group (infected with C. difficile) and SR1001 treatment group (infected with C. difficile+SR1001 treatment). Morphological changes of HT-29 cells were observed. Cell proliferation was detected by CCK-8 assay, expression of PI3K/AKT/mTOR signaling pathway was detected by Western blotting, and TcdB content in the cell supernatant was detected by ELISA. Results: Compared with the control group, cells in CDI group became brighter and rounder, apoptosis was obvious, cell proliferation ability was significantly decreased (P<0.05), and inhibition of cell proliferation increased with the extension of time; the expressions of PI3K/AKT/mTOR pathway phosphorylated proteins and the content of TcdB in the supernatant were significantly increased (P<0.05). After SR1001 treatment, the cells tended to be in normal 'paving stone'-like arrangement, apoptosis was improved, cell proliferation ability was significantly increased than in CDI group, and expressions of PI3K/AKT/mTOR pathway phosphorylated proteins and TcdB content in the supernatant were significantly decreased. Conclusions: SR1001 can reverse the effect of C. difficile on growth of colon cancer cells by interfering the phosphorylation of PI3K/AKT/mTOR pathway.

Association Of Febrile Seizure With Hyponatremia- A Prospective Study

Background & Objective-Febrile seizure is the most common seizure disorder in the pediatric age group and often recurs within the rst twenty four hours. It has been observed that children have lower serum sodium levels was a risk factor for recurrence of febrile seizure. The study was conducted to ascertain the role of serum sodium level in the rst episode of febrile seizure and as a predictor of seizure recurrence within the same febrile illness. Material and methods-It was a prospective observational study conducted at Tertiary medical teaching hospital, in Department of Pediatrics. 55 Children of age 6 months to 60 months presenting with rst episode of seizure with fever in our Hospital were selected for the study. Serum sodium levels were evaluated in all the children. Results-Sr. Sodium level reveals that in 72.73% of the children Sr. Sodium Level was ≤ 135 whereas in 27.27% it was >135 and mean level was 133.49±6.02.Conclusion-Measurement of the serum sodium in a child with febrile seizures helps in predicting seizure recurrence within the same febrile illness.

Characterization of Eudragit types and Kollidon SR inter-polymer complexes and their effects on the drug release

A novel of polymer combination promotes an increase of the ability for controlling the drug release. The objectiveof this research was to characterize the inter-polymer complexes (IPCs) of Eudragit (Eud) types (Eud RS, Eud L, orEud E) and Kollidon SR (KSR), and elucidate their effects on the drug release kinetics and mechanism. Differentpreparation techniques were proposed using spray drying and ultrasonic-assisted anti-solvent techniques. The thermalactivity, e.g., glass transition temperature (Tg) and Fourier transform infrared spectroscopy were used to characterizethe molecular interaction of these IPCs. Theophylline (THP) was selected as a drug model. The effect on the drugrelease kinetics and mechanism was the main concern of this study. Depending on the results, the hydrogen bondingformation between polymers was observed by a shifting of OH and carbonyl group vibrations. In addition, the van derWaals interaction was identified by an alteration in the vibrational band around the 1,000–1,500 cm−1. Meanwhile, thechange of physicochemical characteristic was identified by the Tg of IPCs. Eud E-KSR and Eud E-Eud L IPC wereunable to control the THP release. Meanwhile, Eud L-KSR IPC and Eud RS-KSR IPC were success to control theTHP release, but it was pH dependent and independent, respectively. This study concluded that the IPCs allowed theTHP release in a controlled manner based on the IPC characteristics and their interactions. Either positive or negativeinteractions on the drug release were observed due to native characteristics of polymers.

Formulation, Development And In Vitro Evaluation Of Tramadol Extended Release Tablets

Objective: The objective of the present study was to develop “once daily” extended release tablets of tramadol (100 mg) by wet granulation using hydrophilic polymer like hydroxy propyl methyl cellulose K100M,K15M and polyethylene oxide (PEO). Methods: The tramadol matrix tablets were prepared by using different polymers like hydroxy propyl methyl cellulose (HPMC K15M and K100M), polyethylene oxide (PEO) as the nontoxic and easily available suitable matrix system. The extended release tablets of tramadol (400 mg) were prepared wet granulation technique. Different pre compression and post compression were performed. In vitro dissolution tests were performed and percentage drug release was calculated. The fourier-transform infrared spectroscopy (FTIR) studies conducted on pure drug tramadol and the optimize formulation (T6). Different release models like zero order, first order, higuchi and Korsemeyer-Peppas were applied to in vitro drug release data in order to evaluate the drug release mechanisms and kinetics. Results: Pre compression and post compression parameters satisfied with pharmacopeia specifications. The In vitro release studies were performed using USP type II apparatus showed that optimized formulation T6 consisting of polyethylene oxide (PEO) with 25 mg of the polymer was found to extended release of tramadol over a period of 24h. The optimized formulation T6 followed the zero order kinetics as correlation coefficient (r2) values are higher than that of first-order release kinetics. In order to understand the complex mechanism of drug release from the optimized formulation T6 matrix system, the in vitro release rate were fitted to Korsemeyer-Peppas model and the release exponent value (n) obtained was 0.82105 exhibited anomalous (non fickian) diffusion mechanism. Conclusion: The present study shows that polyethylene oxide was found to play a great role in controlling release of tramadol from the matrix system. Accordingly it can be concluded that the formulation is robust in the performance is less likely to be affected by the various factors studied.

Investigation on 90Sr concentrations in foods near Ningde Nuclear Power Plant in 2013-2017 / 中华放射医学与防护杂志

Objective@#To investigate the 90Sr concentration levels in the monitoring areas and the control area at Ningde Nuclear Power Plant (NPP).@*Methods@#Food samples were collected from the monitoring areas in 30 km of Ningde NPP and the control area far away. The radioactive levels of 90Sr in food samples were analyzed using the chromatography with 2-(2-ethylhexyl) phosphate fast extraction method.@*Results@#In this survey, 90Sr radioactive concentrations in 30 varieties of foods in 6 categories were analyzed. In the monitoring area, 90Sr radioactivity concentration in the samples collected were in the range of 0.017-1.830 Bq/kg for cereals, beans and potatoes, 0.021-0.318 Bq/kg for vegetables, 0.007-7.690 Bq/kg for quatic products, and 0.009-0.184 Bq/kg for meats; whereas, in the control area, cereals, beans and potatoes in 0.017-0.700 Bq/kg, vegetables in 0.034-0.677 Bq/kg, aquatic products in 0.038-3.360 Bq/kg, and meats in 0.019-0.054 Bq/kg.@*Conclusions@#The 90Sr radioactive concentrations in foods were far below the food standard limits in this survey. The contribution of evaluated to the public from the 90Sr in foods was neglectable.

Investigation on 90Sr concentrations in foods near Ningde Nuclear Power Plant in 2013-2017 / 中华放射医学与防护杂志

Objective To investigate the 90Sr concentration levels in the monitoring areas and the control area at Ningde Nuclear Power Plant (NPP).Methods Food samples were collected from the monitoring areas in 30 km of Ningde NPP and the control area far away.The radioactive levels of 90Sr in food samples were analyzed using the chromatography with 2-(2-ethylhexyl) phosphate fast extraction method.Results In this survey,90Sr radioactive concentrations in 30 varieties of foods in 6 categories were analyzed.In the monitoring area,90Sr radioactivity concentration in the samples collected were in the range of 0.017-1.830 Bq/kg for cereals,beans and potatoes,0.021-0.318 Bq/kg for vegetables,0.007-7.690 Bq/kg for quatic products,and 0.009-0.184 Bq/kg for meats;whereas,in the control area,cereals,beans and potatoes in O.017-0.700 Bq/kg,vegetables in 0.034-0.677 Bq/kg,aquatic products in 0.038-3.360 Bq/kg,and meats in 0.019-0.054 Bq/kg.Conclusions The 90Sr radioactive concentrations in foods were far below the food standard limits in this survey.The contribution of evaluated to the public from the 90Sr in foods was neglectable.

Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model

BACKGROUND Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted. OBJECTIVES This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection. METHODS One hundred male Swiss albino mice were divided equally into five groups: healthy uninfected control (group I), infected control (group II), PZQ treated (group III), rimonabant (RIM) (SR141716, a CB1 receptor antagonist)-treated (group IV) and group V was treated with combined PZQ and RIM. Liver sections were obtained for histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining and assessment of CB1 receptor expression using real-time polymerase chain reaction (RT-PCR). FINDINGS The most effective reduction in fibrotic marker levels and granuloma load was achieved by combined treatment with PZQ+RIM (group V): CB1 receptor expression (H = 26.612, p < 0.001), number of α-SMA-positive cells (F = 57.086, p < 0.001), % hepatic portal fibrosis (F = 42.849, p < 0.001) and number of granulomata (F = 69.088, p < 0.001). MAIN CONCLUSIONS Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.

Comparison of Four Automated Carcinoembryonic Antigen Immunoassays: ADVIA Centaur XP, ARCHITECT I2000sr, Elecsys E170, and Unicel Dxi800

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the tumor markers available for evaluating disease progression status after initial therapy and monitoring subsequent treatment modalities in colorectal, gastrointestinal, lung, and breast carcinoma. We evaluated the correlations and differences between widely used, automated CEA immunoassays at four different medical laboratories. METHODS: In total, 393 serum samples with CEA ranging from 3.0 to 1,000 ng/mL were analyzed on ADVIA Centaur XP (Siemens Diagnostics, Tarrytown, NY, USA), ARCHITECT i2000sr (Abbott Diagnostics, Abbott Park, IL, USA), Elecsys E170 (Roche Diagnostics, Indianapolis, IN, USA), and Unicel DxI800 (Beckman Coulter, Fullerton, CA, USA), and the results were compared. Deming regression, Passing-Bablok regression, and Bland-Altman analyses were performed to evaluate the data correlation and % differences among these assays. RESULTS: Deming regression analysis of data from Elecsys E170 and UniCel DxI800 showed good correlation (y=3.1615+0.8970x). According to Bland-Altman plot, no statistically significant bias (−1.78 ng/mL [95% confidence interval: −4.02 to 0.46]) was observed between Elecsys E170 and UniCel DxI800. However, the relative differences of CEA concentrations between assays exceeded the acceptable limit of 30%. Regarding the agreement of positivity with cut-off value 5.0 ng/mL, ARCHITECT i2000sr and Elecsys E170 showed the highest agreement (95.2%), whereas ADVIA Centaur XP and ARCHITECT i2000sr showed the lowest agreement (70.7%). CONCLUSIONS: Agreements between automated CEA immunoassays are variable, and individual CEA concentrations may differ significantly between assays. Standardization of serum CEA concentrations and further harmonization are needed.

Therapeutic effect of 90Sr dynamic therapy in the treatment of pathological scar / 中华整形外科杂志

Objective@#To study the therapeutic effect of surgery combined with 90Sr dynamic therapy used in pathological scar.@*Methods@#323 cases of pathological scar were treated with 90Sr dynamic therapy after surgery from June 2010 to June 2014. Initial treatment regimen was made according to the growth characteristics of pathological scar. Then adjusting the treatment programs according to the treatment response.The treatment effect and complications were compared between the new treatment regimen and traditional regimen used in 252 patients (June 2006 to May 2010). SPSS 17.0 was used for statistical analysis of data. Chi-square test was used for comparison of the differences between groups. The scars Vancouver scores were analyzed by one-way ANOVA two years after treatment. P<0.05 was considered statistically significant.@*Results@#The absorption rate in the proliferative phase of the dynamic treatment group was (4.32±0.00) cGy.s-1.cm-2, which was higher than that in the traditional treatment group (3.24±0.00) cGy.s-1.cm-2(F=1.742, P=0.000). Two years after treatment, the score in the dynamic treatment group was (2.94±1.22) points, which was lower than that in the traditional treatment group (4.21±1.68) (F=93.841, P=0.000); the complication rate and recurrence rate were 0.9% (3/323) and 0.6% (2/323) in dynamic treatment group while 11.1% (28/252) and 9.5% (24/252) in traditional treatment group, respectively. The difference was statistically significant(χ2=457.69, P=0.000; χ2=457.70, P=0.000).@*Conclusions@#The treatment of surgery combined with 90Sr isotope is effective in pathological scar, but treatment programs should be developed as a dynamic treatment according to the individual characteristics of the pathological scar.

Exploring the Factors That Influence Pain Relief and Bone-marrow Suppression When Strontium Chloride Is Administrated

Aim: The usefulness and safety of strontium chloride (89Sr), a radiopharmaceutical agent for painful bone metastasis, varies from patient to patient, but the reasons for why the usefulness and safety vary have not been elucidated. The purpose of this study is to explore the background factors of patients who experienced pain relief or bone-marrow suppression after 89Sr was administrated. Methods: In the cases of pain relief, we divided the results from a numeric rating scale (NRS) before and after 89Sr administration into effective and ineffective groups as outcomes. In the cases of bone-marrow suppression, we analyzed neutrophil cells, blood platelets, and hemoglobin levels, respectively, before and after 89Sr administration as outcomes. Then, we performed statistical analyses on both case groups. Results: The results showed that the background factors associated with pain relief were weight, the 89Sr dosage amount, NRS, eGFR, SCr, and Ca levels before 89Sr administration and the area of bone metastasis (number of sites reached). We found that background factors associated with bone-marrow suppression have a moderate significant correlation with hemoglobin, NRS, and SCr levels before 89Sr administration after investigating factors which influence neutropenia. In the case of thrombocytopenia, there was a moderate significant correlation with platelet counts before 89Sr administration. In the case of hypochromia, there was a moderate significant correlation with hemoglobin levels before 89Sr administration. Discussion: Our study could elucidate patient background factors associated with pain relief and bone-marrow suppression after 89Sr administration.