Tumor-targeting intravenous lipid emulsion of paclitaxel:Characteristics,stability,toxicity,and toxicokinetics / 药物分析学报

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Predictors of long-term efficacy and recurrence of anti-vascular endothelial growth factor therapy for idiopathic choroidal neovascularization / 中华眼底病杂志

Objective:To investigate the clinical effects and influence factors of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs in the treatment of idiopathic choroidal neovascularization (ICNV).Methods:This retrospective study involved 27 patients (27 eyes) with ICNV from July 2012 to July 2015. Patients received intravitreal bevacizumab (1.25 mg), ranibizumab (0.05 mg), additional injection was provided if it was needed. The average follow-up time was 168 weeks. The recovery of best corrected visual acuity (BCVA) and central foveal retinal thickness (CRT) of the affected eye was observed. Follow up once a month after the initial treatment until the lesion was completely absorbed or scarred (the first follow-up period). Follow up every 12 weeks was performed to observe the recurrence of the lesions (the second stage of long-term follow-up). One month after the last injection of the first follow-up period, according to the regression of choroidal neovascularization (CNV), the affected eyes were divided into a significant improvement group (significant improvement group) and an insignificant improvement group (non-significant improvement group)), to analyze the effects of age, course of disease, type of drugs, number of injections, baseline BCVA and CRT on the regression of CNV lesions. According to the results of long-term follow-up, the eyes were divided into recurrence group and non-recurrence group, and the factors affecting the recurrence of CNV lesions were analyzed. Measurement data between groups was compared by using independent sample t test or non-parametric test; count data was compared by using χ2 test. Logistic regression analysis was used to analyze the factors affecting the regression and recurrence of the lesion. Results:At baseline and 1 month after the last injection in the first stage, the average BCVA of the eyes were 55.70±15.21 and 73.59±12.08 letters; CRT was 338.3±89.32 and 264.5±47.47 μm, respectively. The BCVA and CRT of the affected eyes were compared at the two time points, and the differences were statistically significant ( Z= -3.886, -4.061; P<0.001). The BCVA of the eyes in the significant improvement group and the insignificant improvement group were 65.38±17.27 and 51.63±12.61 letters, respectively; the difference between the two groups of BCVA was statistically significant ( t=-2.316, P=0.029). The results of long-term follow-up showed that of the 27 eyes, 6 eyes had recurrence; the average recurrence time was 90.83±49.02 weeks. After another intravitreal injection of anti-VEGF drugs, the CNV lesions was resolved. The average injection times of the relapsed group and the non-relapsed group were 3.67±0.816 and 2.24±0.768, respectively. The average injection times of the relapsed group was significantly higher than that of the non-relapsed group, and the difference was statistically significant ( Z=-3.253, P<0.001). There was no statistically significant difference between the two groups of eyes at baseline and CRT at the last follow-up ( Z=-1.342,-1.313; P=0.195, 0.195). Conclusion:Intravitreal injection of anti-VEGF drugs can effectively increase the regression rate of BCVA and CNV lesions in ICNV eyes; high baseline visual acuity indicates better CNV lesion regression after treatment. Relapsed patients can be effectively improved after re-treatment with anti-VEGF drugs, and CNV recurrence has no significant effect on the final prognosis.

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

A multicenter study of reference intervals for 15 laboratory parameters in Chinese children / 中华儿科杂志

Objective@#To establish comprehensive laboratory reference intervals for Chinese children.@*Methods@#This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex.@*Results@#In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old.@*Conclusion@#This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.

Analgesia,Sedation Effects and Safety of Flurbiprofen Axetil Combined with Hydromorphone for PCIA after Orthopedics Surgery / 中国药房

OBJECTIVE:To observe analgesia,sedation effects and safety of flurbiprofen axetil combined with hydromorphone for postoperative patient-controlled intravenous analgesia (PCIA) after orthopedics surgery. METHODS:Totally 90 patients with combined spinal epidural anesthesia underwent lower limb surgery were selected from anesthesology department in the Affiliated Hospital of Chengde Medical College during May 2016-Jan. 2018. They were divided into SF group,H group and KH group according random number table,with 30 cases in each group. The postoperative PCIA pump drug liquid formula of SF group included Sufentanil citrate injection 2-3 μ g/kg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL;that of H group included Hydromorphone hydrochloride injection 0.12 mg/kg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL;that of KH group included Hydromorphone hydrochloride injection 0.12 mg/kg+Flurbiprofen axetil injection 50 mg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL. The operation time, intraoperative medication (epidural application frequency of additional ropivacaine,frequency of ephedrine and atropine),effective pressing times of analgesic pump and the analgesic effect of PCIA were observed in 3 groups. VAS score and Ramsay sedation score were observed 2,6,12,24,48 h after surgery. The hospital anxiety and depression scale (HAD) score,profile of mood states (POMS) score and the occurrence of ADR were observed before and after surgery. RESULTS:There was no statistical significance in operation time,epidural application frequency of additional ropivacaine or frequency of ephedrine and atropine among 3 groups (P＞0.05). The effective pressing times of analgesic pump in KH group were significantly lower than SF group and H group. The proportion of patients with excellent and good anesthesia effect in KH group was significantly higher than SF group and H group (P＜0.05);there was no statistical significance between SF group and H group(P＞0.05). VAS score of 3 groups 48 h after surgery were significantly lower than 6, 12,24 h after surgery;that of KH group was significantly lower than SF group and H group(P＜0.05);there was no statistical significance between SF group and H group(P＞0.05). There was no statistical significance in Ramsay score among 3 groups at different time points(P＞0.05). Before surgery,there was no statistical significance in HAD score or POMS score among 3 groups (P＞0.05). After surgery,HAD score and POMS score of KH group and H group were significantly lower than before surgery and SF group(P＜0.05);there was no statistical significance in KH group and H group,before and after surgery in SF group(P＞0.05). No vomiting,respiratory depression,pruritus and digestive tract bleeding were observed in 3 groups. The incidence of dizziness and nausea in H group and KH group were significantly lower than SF group (P＜0.05);there was no statistical significance between KH group and H group(P＞0.05). CONCLUSIONS:The flurbiprofen axetil combined with hydromorphone show good analgesic and sedative effect for PCIA after orthopedics operation,and can significantly improve emotion and mood of patients with good safety.

Progress on the construction of adenovirus vectors / 国际儿科学杂志

Adenovirus vectors are widely used in many fields such as in vitro and in vivo gene transduction,gene therapy,vaccination and oncolytic treatment.They have high titer,low pathogenicity,high transduction efficiency,wide infected tissue and no host cell genome integration and many other advantages,and are widely used in experimental and clinical research.In recent years,using different methods of experimental improvement of adenoviral vectors in the basic and clinical research has made great development,becoming the most promising aspect of the viral vectors.This article reviews the structure of adenovirus,the development characteristics of adenoviral vectors and the latest improvements,clinical applications and other aspects of research progress.

Sedative effect of non-intravenous administration dexmedetomidine in pediatric patients underwent lower abdomen and limb surgery / 吉林大学学报(医学版)

Objective:To investigate the application of non-intravenous dexmedetomidine(DEX)in the pediatric patients underwent lower abdomen and limb surgery,and to observe the sedative effect of DEX in this procedure. Methods:Sixty patients undergoing the general anesthesia for lower abdomen and limb surgery were selected and randomly devided into ropivacaine sacral block(RS)group,intranasal DEX+ ropivacaine sacral block(ID)group, ropivacaine + DEX sacral block(DS)group,20 cases in each group.The children in ID group received intranasal DEX 1 μg·kg-130 min before operation and the children in RS and DS groups received physiological saline. 1 mL·kg-1propofol was infused intravenously in the children who could not smoothly enter into the operating room as well as the intolerance to oxygen mask or sevoflurane inhalation while induction.The children in RS and ID groups received 0.25% ropivacaine 1 mL·kg-1,and the children in DS group received the same dose of ropivacaine mixed with 1 μg·kg-1DEX,and the total volume of drugs was 20 mL.The general information of each child was recorded;the sedation status when separated from their parents and induction period mask and sevoflurane acceptance scores were assessed;the satisfaction of separation with parents,oxygen mask and sevoflurane inhalation were recorded;the time of operation,induction,extraction of laryngeal mask and anesthesia awake were recorded;delayed awakening,laryngismus and awakening period agitation score were recorded.The scores of anesthesia recovery and the dosage of propofol were recorded;the sedation scores 4,8,12,16,20,and 24 h after operation were recorded.Results:Compared with RS and DS groups,the sedation scores of the children when they were separated from their parents and mask induction and sevoflurane inhalation acceptance,the satisfaction degree of separation,mask and sevoflurane acceptance in ID group were increased(P<0.05);the dosage of propofol in ID group were decreased(P<0.05).The time of operation,extraction of laryngeal mask and anesthesia awake had no significant differences between three groups(P>0.05),the induction time of children in ID group was shorter than those in RS and DS groups(P<0.05).There was no delayed awakening in three groups,and the laryngismus and the awakening period agitation score in RS group were higher than those in ID and DS groups(P<0.05).There was no differences in the consciousness,respiration,activity scores and the scores of anethesia recovery between three groups(P>0.05).The sedation scores in the three groups were less than 3 points 4 h after operation. Compared with RS group,the sedation scores in ID and DS groups were decreased 8 h after operation(P<0.05). Compared with RS and ID groups,the sedation scores in DS group 12,16 and 20h after operation were decreased (P<0.05).There were no significant differences in the sedation scores between three groups 24 h after operation (P>0.05).Conclusion:When non-intravenous DEX is used in the pediatric patients underwent lower abdomen and limb surgery,the children can quietly and co-operationly enter into the operating room and quickly and smoothly complete the induction process;the incidence of revival restlessness is significantly reduced,and it can play a role in the early postoperative sedation.

Application of acupoint massage in postpartum hypogalactia in puerpera / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the effects of acupoint massage for postpartum hypogalactia in puerpera.</p><p><b>METHODS</b>A total of 60 puerpera of cesarean section were randomized into an observation group and a control group, 30 cases in each one. In the observation group, 2 cases were dropped out. Finally, there were 28 cases in the observation group and 30 cases in the control group. In the control group, the routine nursing after operation in obstetrics department was given, guiding maternal breastfeeding and postpartum health education. In the observation group, on the basis of the treatment as the control group, the corresponding acupoints were selected from the breast related meridians for massage. Acupoint massage was given since the 3rd day after operation, 8:00 am to 9:00 am, once a day, 1 min at one acupoint, continuously for 5 days. The lactation volume, breast filling, galactostasis and milk viscosity were compared in the parturient of the two groups. The clinical therapeutic effects were compared between the two groups.</p><p><b>RESULTS</b>From the 1st to the 2nd days, the differences were not significant in lactation volume, breast filling and galactostasis score between the two groups (all>0.05). From the 3rd to 5th days, the lactation volume, breast filling and galactostasis score in the observation group were all lower than those in the control group (all<0.01). The difference in milk viscosity was not significant in the first 4 days between the two groups (all>0.05). On the 5th day, the score of milk viscosity in the observation group was lower than that in the control group (<0.01). The cured rate was 64.3% (18/28) in the observation group, which was better than 13.3% (4/30) in the control group (<0.05).</p><p><b>CONCLUSION</b>Massage at the acupoints from the breast related meridians effectively promotes the lactation secretion in puerpera of postpartum hypogalactia and alleviates breast distention.</p>

Effects of wild-type PTEN overexpression and its mutation on F-actin in activated hepatic stellate cells / 中华肝脏病杂志

Objective@#To investigate the effect of overexpression of wild-type phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and its mutant G129E (exhibiting the activity of protein phosphatase and losing the activity of lipid phosphatase) on F-actin in activated hepatic stellate cells (HSCs) cultured in vitro.@*Methods@#The activated hepatic stellate cell-T6 (HSC-T6) cells were cultured in vitro, and activated HSCs were transfected with adenovirus that carried wild-type PTEN gene and G129E gene using transient transfection. The HSCs were divided into the following groups: control group, which was transfected with DMEM medium instead of virus solution; Ad-GFP group, which was transfected with the empty adenovirus vector with the expression of green fluorescent protein (GFP); Ad-PTEN group, which was transfected with the recombinant adenovirus with wild-type PTEN gene and GFP expression; Ad-G129E group, which was transfected with the recombinant adenovirus with G129E gene and GFP expression. Western blot and quantitative real-time PCR were used to measure the protein and mRNA expression of PTEN in activated HSCs; under a laser scanning confocal microscope (LSCM), phalloidine labeled with the fluorescein tetramethylrhodamine isothiocyanate (TRITC) was used to observe the morphology of HSCs, distribution and fluorescence intensity of F-actin, and changes in pseudopodia and stress fibers, and a calcium fluorescence probe (Rhod-2/AM) was used to measure the changes in Ca2+ concentration in HSCs. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference test was used for comparison between two groups.@*Results@#Wild-type PTEN and G129E genes were highly expressed in activated HSCs. In the control group and the Ad-GFP group, HSCs had a starlike or polygonal shape, F-actin was reconfigured and formed a large number of stress fibers which stretched across the whole cell, and layered pseudopodia were seen around the cell. In the Ad-PTEN group and the Ad-G129E group, the HSCs had a fusiform shape, F-actin was mainly seen around the cell, a small number of stress fibers were seen inside the cell, and layered pseudopodia around the cell disappeared. The Ad-PTEN group and the Ad-G129E group had significant reductions in the fluorescence intensity of F-actin compared with the control group and the Ad-GFP group (357.67±13.39/377.25±14.55 vs 961.87±27.33/954.68±20.71, F = 1783.486, P < 0.05), while there were no significant differences between the Ad-PTEN group and the Ad-G129E group, as well as between the control group and the Ad-GFP group (P > 0.05). The Ad-PTEN group and the Ad-G129E group had significant reductions in the relative concentration of Ca2+ compared with the control group and the Ad-GFP group (251.60±90.88/352.18±146.01 vs 1953.95±132.99/1937.57±115.17, F = 834.988, P < 0.05), while there were no significant differences between the Ad-PTEN group and the Ad-G129E group, as well as between the control group and the Ad-GFP group (P > 0.05).@*Conclusion@#The overexpressed wild-type PTEN and its mutant G129E can significantly inhibit the formation and reconfiguration of cytoskeletal protein F-actin and reduce the concentration of Ca2+ in activated HSCs in vitro. In addition, there are no significant differences in the above effects between wild-type PTEN and G129E.

Detection of Related Substances and Preliminary Study on the Degradation Mechanism of Baicalein / 中国药房

OBJECTIVE:To establish a method for the separation and detection of related substances in baicalein,identify its structure and preliminarily explore the degradation mechanism. METHODS:HPLC was adopted to detect the baicalein,related impurities and forced destruction of degradation products in synthesis process:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid-methanol-acetonitrile(gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,the column temperature was 10℃,and the injection volume was 10μL. LC-MS/MS was conducted to identify the related substances and conjecture degradation mechanism:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid- methanol (gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,column temperature was 10℃,and the injection volume was 10μL;ion source was electrospray ion source,positive and negative ions,nebulizer pressure was 55 psi and the drying gas flow was 11 L/min,drying gas temperature was 350℃,capillary voltage was 4.0 kV,detection modes were full-scan first-order MS and selective ion full-scan second-order MS,scan ranges were m/z 100-1000 (first-order MS) and 50-500(second-order MS),ionization voltage was 80-135 eV,and the collision energy was 10-30 eV. RESULTS:The linear range of baicalein was 2.4-480μg/mL(r=0.9999);RSDs of precision,stability and reproducibility tests were lower than 2.0%;the limit of quantitation was 7.2 ng,the limit of detection was 2.4 ng. Baicalein was well separated with related substance and 3 major degradation products,the related substance was chemical synthesis precursor wood butterfly;the degradation products were 6,7-quinone derivatives and 7,8-quinone derivatives,which were isomers;oxidative degradation products were benzoic acid phenyl ester derivatives. CONCLUSIONS:The main mechanisms of alkali degradation and oxidative degradation of baicalein include pyran, reciprocal rearrangement and oxidation reaction;the established method is specific and sensitive,and can be used for the detection of related substances in baicalein.

Percentage of primary open angle glaucoma in retinal vein occlusion patients / 中华实验眼科杂志

Background Researches determined that the pathogenesis of retinal vein occlusion (RVO) is associated with primary open angle glaucoma (POAG) in Caucasian population.However,the relationship between RVO and POAG in Asian population is unclear.Objective This study was to survey the percentage of POAG in RVO patients in China.Methods A prospective cross-sectional observational study based on hospital was performed.Three hundred and seventy five patients with newly diagnosed RVO by fluorescein fundus angiography (FFA) were consecutively enrolled in Peking University Third Hospital from October 2011 to May 2013,and gonioscopy was carried out in all the patients.Glaucoma was diagnosed according to the criteria of the International Society of Geographical and Epidemiological Ophthalmology (ISGEO).RVO was classified into central retinal vein occlusion (CRVO),hemicentral retinal vein occlusion (HRVO) and branch retinal vein occlusion (BRVO) based on fundus photograph and FFA,or classified into arteriovenous crossing RVO (AV-RVO),optic cup RVO (OC-RVO),optic nerve RVO without optical nerve head swelling (NONHS-RVO) and RVO with optical nerve head swelling (ONHS-RVO) based on the sites of venous occlusion.The percentages of POAG in different types of RVO were calculated.This study was approved by Ethic Committee of Peking University Third Hospital,and written informed consent was obtained from each patient before entering study cohort.Results Three hundred and seventeen RVO patients finished screening of glaucoma,with the response rate 84.5％.The percentage of POAG is 8.2％ in RVO patients,including 7.1％ in the CRVO patients,23.5％ in HRVO patients and 6.2％ in BRVO patients.The percentage of POAG was significantly higher in OC-RVO patients (27.9％) and NONHS-RVO patients (13.2％) than that in AV-RVO patients (4.7％) and ONHS-RVO patients (1.3％) (all at P＜0.05).Conclusions The overall percentage of POAG in RVO patients in China is 3-4 times higher than general population.Higher percentage of POAG is found in OC-RVO patients and NONHS-RVO patients,suggesting that pathogenesis of RVO is probably associated with the glaucomatous anatomic changes of optical nerve head.

The clinical detection significance of serum miR-137 in central precocious puberty girls / 实用医学杂志

Objective To investigate the clinical significance of testing serum kisspeptin in central precocious puberty (CPP) girls. Methods Sixty eight CPP girls and 68 healthy girls was studied from December 2012 to December 2014. HEK293 cells were cultured. Luciferase reporter assay was performed to verify the binding of miR-137 to the 3′UTR of KISS1. Serum miR-137 level was levaluated by qRT-PCR. Level of serum luteinizing hormone , prolactin , follicle stimulating hormone , thyrotropin , free thyroxine and estradiol was evaluated by chemi-luminescence immunoassay. The level of serum kisspeptin was detected by ELISA. Results MiR-137 was confirmed to bind to the 3′UTR of KISS1. The level of serum miR-137 was downregulated and kisspeptin was enhanced in CPP girls. The expression of miR-137 and kisspeptin was negatively correlated. Serum miR-137 level was negatively related to bone age and bone age advancement. According to the results of GnRH stimulating test, serum miR-137 was related to peak LH and peak/basal LH ratio. Conclusions MiR-137 could bind to the 3′UTR of KISS1. MiR-137 may be a potential biomarker for CPP assisted diagnosis.

Genistein antagonizes paraoxon-induced high expressions of NADPH oxidase p22phox and Nox4 in rat thoracic aorta tissues / 中国药理学通报

Aim To investigate whether genistein pro-tects paraoxon-induced vascular endothelial dysfunction through down-regulating p22phox and Nox4 expressions as well as inhibiting the generation of ROS.Methods In this study,thoracic aortas were isolated from the male Sprague-Dawley(SD)rats and were divided into the following groups:① control group,the thoracic a-ortas were incubated with dimethyl sulfoxide (DMSO, 0.1%)for 30 min;② genistein group,the thoracic a-ortas were incubated with genistein(100 μmol·L -1 ) for 30 min;③ paraoxon group,the thoracic aortas were incubated with paraoxon at the concentration of 40.5 μmol · L -1 for 30 min; ④ paraoxon plus genistein groups,the thoracic aortas were incubated with paraoxon (40.5 μmol·L -1 )plus genistein (100μmol·L -1 )for 30 min.The expressions of p22phox and Nox4 mRNA were detected by RT-PCR and the protein expressions ofp 2 2 phox and Nox4 were detected by Western blot.Results Compared with the control group,the expressions of p22phox and Nox4 were markedly increased in the paraoxon group. In the genistein group,the expressions of p22phox and Nox4 were significantly repressed. When treated with genistein plus paraoxon,there was a marked increase in the expression of Nox4(P <0.05),but no signifi-cant difference in the expression of p22phox.The ex-pression of p22phox in the paraoxon plus genistein group was significantly decreased(P <0.05)as com-pared with paraoxin group,but there was no significant difference in the expression of Nox4.Conclusion Paraoxon may result in oxidative damage of vascular endothelium through up-regulating p22phox and Nox4 expressions,genistein may down-regulate the expres-sions of both and protect vascular endothelium.

Targeted monitor and comprehensive intervention of multidrug-resistant organism infection in a general hospital / 中国感染控制杂志

Objective To evaluate the occurrence of multidrug-resistant organism (MDRO)infection in a general hospital,and take effective comprehensive intervention measures,so as to reduce MDRO infection.Methods Targeted monitoring on MDROs was performed from October 2012 to December 2013,comprehensive intervention measures were conducted,the occurrence of MDRO infection before and after intervention was compared.Results A total of 62 384 pa-tients were investigated,17.91%(n=11 176)were sent specimens for pathogen culture,606 times of culture for patients’ specimens were detected MDROs,292(0.47%)cases were MDRO healthcare-associated infection(HAI),314 were com-munity-acquired infection or colonization.MDRO infection case rate decreased from 0.65%(75/11 603)before intervention to 0.26%(36/13 875)after intervention (χ2 =21.08,P <0.05).Conclusion Comprehensive intervention measures can effectively reduce the occurrence of MDRO HAI.

Etiological analysis of asymptomatic hematuria in 431 children and follow-up / 临床儿科杂志

ObjectiveTo investigate the etiology and prognosis of asymptomatic hematuria in children.MethodsThe etiological factors, clinical features and prognosis of asymptomatic hematuria were analyzed retrospectively in 431 children from Jan. 2001 to Dec . 2014. ResultsIn 431 children (197 males and 234 females) with asymptomatic hematuria, the mean age of ifrst visit was 5.52±2.77 years (8 months-17 years). Four hundred and twenty-ifve cases had persistent microscopic hematuria and 6 cases had gross hematuria. Three hundred and iffteen cases (73.1%) were glomerular hematuria, among which 286 cases were isolated hematuria, 5 cases were acute glomerulonephritis, 13 cases were minimal change glomerulopathy, 4 cases were IgA nephropathy, 4 cases were mesangial proliferation glomerulonephritis and 3 cases were thin basement membrane nephropathy. One hundred and thirty-six cases (31.5%) were non-glomerular hematuria, among whom 113 cases were left renal vein entrap-ment syndrome, 17 cases were idiopathic hypercalciuria, 4 cases were kidney stone, 1 case was urinary tract infection and 1 case was left kidney absence. The mean follow-up period was 3.05±2.69 years (0.5-13.5 years). One hundred and forty-ifve patients showed the resolution of microscopic hematuria, among whom 110 cases (75.8%) had the resolution in 3 years after the ifrst visit. In 24 cases with family history of hematuria, only 6 cases showed the resolution. At the end of the follow-up, renal function remained stable in all children.ConclusionsThe onset age of asymptomatic hematuria in children varies widely, and most of them are glomerular hematuria. Most children with isolated hematuria show resolution within three years after the ifrst visit. The children with familial hematuria may last longer. The isolated hematuria has good prognosis but needs to be followed up.

Exploration of Reform of Experiment Teaching Mode in Pharmaceutical Analysis for Pharmacy Major in Sec-ondary Vocational Education School / 中国药房

OBJECTIVE:To investigate the reform mode of experiment teaching in pharmaceutical analysis in the new situation of vocational education and provide reference for improving the teaching quality of secondary vocational education. METHODS:The present situation of experiment teaching in pharmaceutical analysis was assessed deeply and in detail,and the problems exist-ing in teaching were analyzed;the reform plan and measures according to the disadvantages of the current teaching were raised. RE-SULTS:The experiment teaching in pharmaceutical analysis existed some problems,involving lagging textbook compilation,single teaching mode,“heavy theory,light practice”for time arrangement,obsolete laboratory apparatus and lack of advanced equipments. So a series of measures were adopted,including writing supplementary teaching materials and experimental guidance;reforming the contents of the experiment teaching;reforming the model of teaching and improving the students’participation;reforming the time arrangements;increasing the investment in laboratory equipment and attaching great importance to extramural cooperation;estab-lishing the virtual laboratory;and establishing a flexible,comprehensive and effective experimental evaluation mechanism.CON-CLUSIONS:Reform experimental teaching mode has fully mobilized the enthusiasm and initiative of students and improved the abil-ity of operating skills,and cultivated the strict scientific research style of students. The reform mode of experimental teaching in pharmaceutical analysis is in accordance with the students’learning needs of pharmaceutical majors,and lay a good foundation for the students better and faster adaption to the job.

Effect of bazedoxifene on endometriosis in a rat model / 中华妇产科杂志

Objective To investigate the therapeutic mechanism of bazedoxifene, the third-generation selective ER modulator (SERM), on endometriosis lesions in a rat model. Methods Endometriosis was induced by transplanting pieces of endometrium from other syngeneic rats that were as donors onto the subcutaneous of other unmated female rats. The rats with successful ectopic implants were divided into two groups:control group (n=10) and bazedoxifene group (n=10). The macroscopic morphology, volume, histopathology of ectopic implant and rats uterine wet weight were determined before and after the treatment. Expression of proliferation cell nuclear antigen (PCNA), ER and PR in the eutopic endometrium and endometriosis lesions detected by immunohistochemistry in the two groups. Results (1) The gross morphology and histological changes of endometriosis lesions in rats after treatment: compared with the control group, it was obviously depauperated and had more less glands and blood vessels in the stroma. (2) The change of rats′weight, the volume of endometriosis lesion before and after treatment and rats uterine wet weigh after treatment respectively in the control group and the bazedoxifene group:rats′ weight were respectively before treatment: (201±17) g, (202±18) g, that were respectively after treatment: (266±16) g, (261±16) g, which showed no significant difference between two groups before and after treatment (P>0.05). The volume of ectopic implant before treatment were respectively (85±17) mm3, (85±12) mm3, and showed no significant difference between two groups;that were respectively (48±11) mm3, (24±9) mm3 afte rtreatment, which was significantly decreased compared with the control group (P0.05). Conclusion Bazedoxifene could obviously reduce the size of endometriosis lesions, the mechanism may be related with suppressing estrogen-induced proliferation, the expression of ER and direct ER antagonism by this SERM.

Clinical and prognostic analysis of 27 pediatric patients with bronchiectasis caused by Mycoplasma pneumonia and Chlamydia pneumonia / 临床儿科杂志

Objective To explore the clinical characteristics, treatment and prognosis of pediatric patients with bronchiec-tasis caused by Mycoplasma pneumonia (MP) and Chlamydia pneumonia (CP). Methods The clinical data from 27 MP and CP pneumonia pediatric patients with bronchiectasis suggested by the high resolution CT were retrospectively analyzed. Results The morbility rate of bronchiectasis caused by MP and CP pneumonia is 0.56%. The mean age of these patients was 75.4 ± 52.7 months. Among them, 27 cases (100%) had cough, 19 cases (70.4%) had fever, 10 cases (37%) had respiratory distress and 20 cases had lung auscultation. Sixteen cases were MP-IgM positive, 5 cases (18.5%) were CP-IgM positive and 6 cases (22.2%) were positive of both. Eight cases were combined with other pathogens infections, in which 6 cases were bacterial infections. The imaging ifndings showed diffuse bronchiectasis in 13 cases (48.1%) and local bronchiectasis in14 cases (51.9%). The bronchoscopy found endothelium in-lfammation, mucosal swelling, partial erosion and follicular hyperplasia in 16 cases (66.7%), the formation of short column sputum bolt in 5 cases (20.8%), in which 1 case had plastic bronchitis. All patients were treated with macrolides antibiotics, 10 cases (37%) combined with methylprednisolone, 3 cases (11.1%) combined with immunoglobulin and 20 cases (74%) combined with other anti-biotics. The average length of hospitalization was 12±4.3 days. The bronchiectasis sign disappeared within 4 months in 23 cases (92%). Two cases (8%) still had bronchiectasis after 9 to 15 months, with the recurrent pneumonia. Conclusions MP and CP pneumonia can lead to acute bronchiectasis. Most of patients are recoverable with effective treatment.

Five years change of bacterial spectrum and drug resistance in PICU / 中国小儿急救医学

Objective To analyze the five years change of bacterial infection adn drug resistance in PICU and to provide evidence for use of na tibiotics rationally.Methods Al the pathoeg nic bacteria from patients in PICU of our hospital from January 1 2009 to Deec mber 31 2013 were analyzed retrospectiev ly. T hey were divided into five subgroups according to differetn years.Pathogenic batc eria and drug resistance in different years wre e collected na d the changes of such bacterial infection and drug resistance were compared and summarized.Results A total of 2 201 pathogenic bacterial strains were isolated from 14 361 specimens of five-year patients in PICU.The rate of gram negative bacteria in 2009 to 2013 were 83.2%,71.0%, 59.8%,58.9%, 52.5% respe ctively.The rate of gram positive bacteria in 2009 to 2013 were 16.8%, 29.0%,40.2%, 41.1%, 47.5% respectively.Top five pathogenic bacteria were staphylocco cus aureus (16.6%,366 strains),Escherichia coli (16.2%,357 strains),klebsiella pnue moniae (15.2%,334 strains), streptococ us pneumoniae (9.2%,202 strains),haemophilus influenzae (6.8%,149 strains).The infection rate of staphylococcus aureus increased year by year(6.4% to 27.0%).Drug sensitivity tets indicated that the rate of extended-spectrum beta-lactamases ( ESBL) positive escherichia coli and klebsiella pneumoniae were 28.3%and 38.3%,respectivle y.The rate of methicillin-resistant staphylococcus aureus ( MRSA) was 26.0%.Based on non-meningitis criterion,rate of penicillin resistance streptococcus pneumonia and multiple-drugresistance streptococcus pneumonia was 19.3%and 58.9%,respectively.There were no obvious changes in resistance rate of above-mentioned bacteria during the recent five years.Conclusion In the recent five years,gram negative bacteria is still the prevalent strain in PICU of our hospital,however the rate of gram positive bacteria increases year by year and staphylococcus aureus has become one of the five most common bacteria.The rate of ESBL positive escherichia coli,ESBL positive klebsiella pneumonia and MRSA has no obvious changes.Analysis of pathogenic bacteria and drug-resistance surveillance are of vital importance to guide treatments for critically ill patients and reduce drug-resistant bacterial strains.

Analysis of disease spectrum in Epstein-Barr virus infected children in Zhongshan / 临床儿科杂志

Objective To study the epidemic characteristics and disease spectrum of Epstein-Barr virus (EBV) infected children in Zhongshan region, Guangdong province. Methods Clinical data from the children with positive EBV-DNA detected by real-time lfuorescent quantitative PCR between 2011 and 2013 was retrospectively analyzed. Results A total of 409 cases were detected with EBV-DNA positive from 3402 cases, with a total positive rate 12%, and the positive rate is 8.1%in 2011, 10.4% in 2012, 19.5% in 2013, there were significant differences among positive rate (χ2=6804.00, P0.05) and different age groups (χ2=136.96, P<0.05). The positive rate of pre-school group is the highest. EBV infection can cause multiple system diseases. The most common disease caused by EBV infection was infectious mononucleosis (61.6%), followed by respiratory tract infection (26.7%), neck lymphadenitis (3.4%), idiopathic thrombocytopenic purpura (2.4%), etc. Among the 409 cases of EBV infection, the concurrent other pathogen speciifc IgM positive cases as MP-IgM positive (n=79), CP-IgM positive (n=47), Parvovirus B19-IgM positive (n=20), HSV-IgM positive (n=11), CMV-IgM positive (n=10), and RV-IgM positive (n=4) were found. Conclusions Infectious mononucleosis is the leading disease in children infected by EBV in Zhongshan region, the annual positive rate is increasing. Multiple pathogen speciifc IgM may be detected positive in children with EBV infection, which should be interpreted in combination with clinical status.