60 years old). 43 cases of antiepileptic drugs combination accounted for 10% and the therapeutic plasma concentration of 27 cases deviated from normal range(62.8%). CONCLUSION:Results of plasma concentration monitoring provide an important basis for clinical drug use. Monitoring data and other clinical index can promote rational use of antiepileptic drugs.

Objective To understand the status and main causes of death among children under five years old in Yuyao County from 2013 to 2017, and to provide scientific basis to formulate relevant intervention measures． Methods Data monitoring deaths among children under five years old from 2013 to 2017 in Yuyao were collected. Trend of death, death rank, regional difference and utilization of pre-death health care services for children under 5 years old were retrospectively analysed using SPSS 18.0. Results From 2013 to 2017, the mortality rate in newborns, infants, 1-4 years old children and children under 5 years old (U5MR) decreased in Yuyao county(P=0.016, 0.002, 0.038, ＜0.001). Based on monitored 263 cases of deaths,the majority of deaths of children under 5 years old occurred in infants, accounting for 68.82% (181/263). Congenital malformation and unintentional injury were the main causes of death for children under 5 years old. The deaths of children under 5 years old mainly occurred in medical institutions, and 93.54% of the children were treated before death. The mortality rate of boys under 5 years old was 10.50‰, which was 1.54 times of the mortality of girls ( χ2=11.693, P<0.001). The trend Chi-square test showed that the U5MR in local residents had no obvious downward trend in the past 5 years ( χ2trend =0.195, P=0.658), while the U5MR in floating population significantly decreased with fluctuation ( χ2trend =17.706, P<0.001). Conclusion The key to reduce U5MR in Yuyao is to reduce infant mortality, and the key content of death intervention is to prevent congenital malformations and unintentional injuries. Improving maternal and child health care and developing safety education for migrant children are two effective measures to reduce U5MR.

Objective To investigate the macular vascular density after successful repair of rhegmatogenous retinal detachment (RRD) for one year using optical coherence tomography angiography (OCTA),and discuss the correlation between the macular vascular density and visual acuity.Methods Totally 42 patients of the RRD (42 eyes),their contralateral eyes (A group) and 42 patients of the normal eyes (B group) were recruited into this study.All participants underwent examination with best corrected visual acuity (BCVA) and OCTA.The difference in macular vascular density was compared and the correlation between BCVA and the vascular density was analyzed.Results The macular vascular density of superficial layer,deep layer and choroidal capillary layer was 0.422 4 ±0.089 3,0.4836 ±0.0748,0.527 1 ±0.039 0 in RRD group,respectively,0.469 3 ±0.112 5,0.550 0 ±0.074 0,0.546 2 ±0.034 3 in A group,respectively,0.5619 ±0.053 7,0.611 2 ±0.035 2,0.562 6 ±0.030 4 in B group,respectively.The macular vascular density was significantly decreased in RRD group when compared with A and B groups (all P ＜ 0.05).There was a positive correlation between BCVA and the macular vascular density in the deep layer and choroidal capillaries layer (r =0.629,0.654,both P =0.000).However,there's no correlation between the macular vascular density of superficial layer and BCVA (P =0.103).Conclusion All the macular vascular densities are decreased in patients of RRD after successful repair of retinal detachment one year later,which indicated that the blood flow does not completely recover.And there is a positive correlation between BCVA and macular vascular densities in deep layer and choroidal capillaries layer.And meanwhile,OCTA can objectively and effectively quantify the status of macular region blood flow.

It is a challenging and important project to prolong the in vivo half life of protein and peptide drugs by physicochemical methods without new molecular entities generation. Protein crystallization provides a new strategy for improving the stability and in vivo delivery of these drugs. We show here that recombinant human interferon-alpha (rhIFN) can form spherical crystals. The physical and chemical features of the crystals were characterized, and drug dissolution was determined in vitro. The pharmacokinetics of crystallized interferon after sc injection in rabbit at 1.5 x 10(7) U x kg(-1) was compared to that of soluble form. The crystals were characterized as mono-dispersed spheres, with yield of > 80%, mean diameter size of about 16 microm and crystallinity of 23.2%. The in vitro dissolution behavior of crystallized rhIFN was featured as low initial burst release (21% within the first 2 h) and prolonged cumulative dissolution time up to 72 h without biological potency lost. After sc administration of soluble and crystallized interferon in rabbits, the peak time (T(max)) and half life (t1/2) were prolonged from (1.80 +/- 0.45) h and (1.35 +/- 0.35) h to (13.20 +/- 2.68) h and (10.68 +/- 1.97) h, respectively. The corresponding peak concentration decreased from (1 411.10 +/- 575.28) U x mL(-1) to (721.37 +/- 206.55) U x mL(-1). PK/PD analysis indicated that (96.87 +/- 20.30) % of relative bioavailability was obtained. The research results of this work will provide important academic value and application prospect for improving clinical therapeutic effect and development of biomacromolecules delivery system for protein and peptide drugs.
Animals ; Antiviral Agents ; administration & dosage ; chemistry ; pharmacokinetics ; Biological Availability ; Crystallization ; Delayed-Action Preparations ; Drug Delivery Systems ; Half-Life ; Humans ; Injections, Subcutaneous ; Interferon-alpha ; administration & dosage ; chemistry ; pharmacokinetics ; Male ; Rabbits ; Recombinant Proteins ; administration & dosage ; chemistry ; pharmacokinetics ; Solubility ; Surface Properties

OBJECTIVETo investigate the changes of drug sensitivity of spindle poison-induced polyploid tumor cells to chemotherapeutic agents and its possible mechanism.

METHODSNocodazole in a dose of 100 ng/ml was used to induce polyploidization in a breast cancer cell line MDA-MB-231 cells. The polyploid cells (T-MDA-MB-231) were sorted by flow cytometry. The morphological changes and proliferation of T-MDA-MB-231 cells were compared with that of MDA-MB-231 cells. The cell growth inhibition was assessed by MTT assay. The cells were treated with paclitaxel, docetaxel, vincristine, epirubicin, 5-Fu, VP16 and oxaliplatin, respectively. Those cells were labeled with annexin V-FITC/PI and analyzed by flow cytometry. Bcl-2 was knocked down in T-MDA-MB-231 cells using SiRNA and their growth inhibition was evaluated by MTT assay to evaluate the reversing effect of Bcl-2-silencing on drug resistance.

RESULTSThe polyploid T-MDA-MB-231 cells grew in vitro continuously and maintained constant DNA content. They had a larger cell size, and grew more slowly than MDA-MB-231 cells. The IC(50(s)) of T-MDA-MB-231 cells were significantly higher than that of the MDA-MB-231 cells: paclitaxel: (6.37 ± 0.07) vs. (2.05 ± 0.83) µmol/L; docetaxel: (32.98 ± 1.48) vs. (11.95 ± 0.98) µmol/L; vincristine: (35.28 ± 1.66) vs. (14.58 ± 0.94) µmol/L; oxaliplatin: (19.07 ± 0.45) vs. (9.75 ± 1.05) µmol/L; 5-Fu: (85.49 ± 3.21) vs. (31.35 ± 1.51) µmol/L; and epirubicin: (0.53 ± 0.06) vs. (0.15 ± 0.01) µmol/L, (all P < 0.05). The IC(50(s)) of VP16 in T-MDA-MB-231 cells was (2.85 ± 0.50)µmol/L, significantly lower than the (12.20 ± 1.55) µmol/L in MDA-MB-231 cells (P < 0.05), and that of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (19.59 ± 0.48) µmol/L, significantly higher than the (12.20 ± 1.55) µmol/L in the MDA-MB-231 cells (P < 0.05). The IC(50(s)) of docetaxel of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (21.52 ± 0.68) µmol/L, significantly decreased and lower than that before Bcl-2 silencing (32.98 ± 1.48) µmol/L.

CONCLUSIONSOur results indicate that polyploid tumor cells induced by spindle poison Nocodazole are more resistant to most of chemotherapeutic drugs. Downregulation of Bcl-2 increases the sensitivity of polyploid cells to docetaxel. The high expression of Bcl-2 may be one of the drug resistance mechanisms of polyploid tumor cells. The polyploid tumor cells are relatively sensitive to VP16, suggesting that VP16 might be an effective candidate drug for treatment of chemoresistant polyploid tumors.

Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Down-Regulation ; Drug Resistance, Neoplasm ; Epirubicin ; pharmacology ; Etoposide ; pharmacology ; Female ; Fluorouracil ; pharmacology ; Gene Knockdown Techniques ; Humans ; Inhibitory Concentration 50 ; Nocodazole ; pharmacology ; Organoplatinum Compounds ; pharmacology ; Paclitaxel ; pharmacology ; Polyploidy ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Taxoids ; pharmacology ; Vincristine ; pharmacology

OBJECTIVETo clarify the diagnosis of one suspected case of diphtheria in Guangdong province by epidemiological analysis and etiologic detection.

METHODSOn July 6th 2010, the corynebacterium diphtheria was detected from the nasal secretions of one nasopharyngeal carcinoma patient in a college-town hospital in Guangzhou City, Guangdong Province. The patient and the close contacts were asked to participate in the epidemiological survey; and their nasopharyngeal swabs (3 samples) and the nasal secretions of the patient (1 sample) were collected. The bacteria of the samples were isolated and cultured by blood plate and agar loefflera. The smears of positive strains were dyed and identified by BioMerieux API Coryne biochemical card. Gene tox of β-Corynebacteriophage, Corynebacterium diphtheriae was tested by PCR method, the aliphatic acid was analyzed by gas chromatography method and the Corynebacterium diphtheriae (CMCC 38009) was selected as positive control.

RESULTSThe patient had not gone out, neither had been visited. The patient denied history of vaccines or the immunizations. From the survey on patient's family members and close contacts, no similar symptoms had been found. One strain of Corynebacterium diphtheriae was isolated from the patient's nasal secretions, Gram positive and shape diversified. After cultured by agar loefflera and Gram-dyed and Neisser-dyed, one end or both two ends of the strain showed typical metachromatic granule. API Coryne was identified to Corynebacterium diphtheriae mitis/belfanti (99.4%). The result of gas chromatography method also indicated Corynebacterium diphtheriae. No Corynebacterium diphtheriae was isolated from the nasopharyngeal swabs, neither of the patient nor of the close contacts. The gene tox of β-Corynebacteriophage, Corynebacterium diphtheriae was negative according to the PCR test.

CONCLUSIONThe isolated Corynebacterium diphtheriae did not produce toxin as there was no biological structure gene of toxin. The patient was a health carrier of nontoxic Corynebacterium diphtheriae.

China ; epidemiology ; Corynebacterium diphtheriae ; isolation & purification ; Diphtheria ; epidemiology ; microbiology ; Female ; Humans ; Middle Aged ; Nasopharynx ; microbiology ; Polymerase Chain Reaction ; methods

OBJECTIVETo study the effect of hydroquinone on apoptosis of bone marrow mononuclear cells, and to evaluate the toxic effect of benzene on stem cells.

METHODSCell morphology was observed by HT fluorescent stain method, and DNA fragments were analyzed by agarose gel electrophoresis. Anti-Annexin V FITC plus PI staining for apoptotic and necrotic rate was examined by flow cytometer.

RESULTSAfter adding different concentrations of hydroquinone to the cells for 6 h culture, the fluorescent intensity of nucleus increased, the color of nucleus became deep and inhomogeneous, and the chromatin was condensed and distributed around the neucleus. DNA ladder was detected in all samples. Cell apoptotic rate in different concentration of hydroquinone groups was significantly higher than that in blank control group (P < 0.05). With the increase of the concentration of hydroquinone, the apoptotic and necrotic rate also increased. The optimal concentration of hydroquinone was 50 micro mol/L. When it was >or= 75 micro mol/L, the necrotic rate increased significantly. Hydroquinone-induced apoptosis was associated with culture time at the concentration of 50 micro mol/L, and the peak apoptotic time was 10 h, then the apoptotic rate decreased and necrotic rate increased.

CONCLUSIONHydroquinone can induce apoptosis of bone marrow mononuclear cells in vitro with dose-effect and time-effect relationship.

Apoptosis ; drug effects ; Bone Marrow Cells ; cytology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Hydroquinones ; pharmacology ; Leukocytes, Mononuclear ; cytology ; drug effects ; Mutagens ; pharmacology

BACKGROUNDThe risk of radial artery occlusion (RAO) needs particular attention in transradial intervention (TRI). Therefore, reducing vascular occlusion has an important clinical significance. The aim of this study was to determine the appropriate puncture site during TRI through comparing the occurrence of RAO between the different puncture sites to reduce the occurrence of RAO after TRI.

METHODSWe prospectively assessed the occurrence of RAO in 606 consecutive patients undergoing TRI. Artery occlusion was evaluated with Doppler ultrasound in 2 days and 1 year after the intervention. Risk factors for RAO were evaluated using a multivariate model analysis.

RESULTSOf the 606 patients, the RAO occurred in 56 patients. Compared with TRI at 2-5 cm away from the radius styloid process, the odds ratio (OR) for occlusion risk at 0 cm and 1 cm were 9.65 (P = 0.033) and 8.90 (P = 0.040), respectively. The RAO occurred in the ratio of the arterial diameter to the sheath diameter ≤1 (OR = 2.45, P = 0.004).

CONCLUSIONDistal puncture sites (0-1 cm away from the radius styloid process) can lead to a higher rate of RAO.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01979627; https://clinicaltrials.gov/ct2/show/NCT01979627?term = NCT01979627 and rank = 1.

Aged ; Arterial Occlusive Diseases ; etiology ; Cardiac Catheterization ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Punctures ; Radial Artery

Objective: To observe the lumen structural changes of radial artery (RA) in patients with transradial coronary intervention and the impact of nitroglycerin on the structure by optical coherence tomography (OCT). Methods: A total of 20 patients with transradial coronary intervention were enrolled for OCT imaging to observe and compare the lumen structures of RA between the basic condition and nitroglycerin treated condition. Results: OCT imaging found that 15/20 patients had radial spasm and 1 had intimal tear. Compared to basic condition, with nitroglycerin treatment, the mean lumen diameter, lumen area and total vascular area were increased in the distal, middle and proximal portion of RA, all P<0.001; the intima-media thickness was decreased in the distal, middle and proximal portion of RA, all P<0.001; while the cross section area of tunica media, intimal thickness and extravascular membrane thickness were similar between the basic condition and nitroglycerin treated condition, all P>0.005. Conclusion: Vasodilatation drug may obviously enlarge RA lumen area and total vascular area in patients after transradial coronary intervention.

BACKGROUNDSeveral studies have demonstrated that primary percutaneous coronary intervention (PCI) can result in reperfusion injury. This study aims to investigate the effectiveness of liposomal prostaglandin E1 (Lipo-PGE1, Alprostadil, Beijing Tide Pharmaceutical Co., Ltd.) for enhancing microcirculation in reperfusion injury. In addition, this study determined the optimal administration method for acute ST elevation myocardial infarction (STEMI) patients undergoing primary PCI.

METHODSTotally, 68 patients with STEMI were randomly assigned to two groups: intravenous administration of Lipo-PGE1 (Group A), and no Lipo-PGE1 administration (Group B). The corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and myocardial blush grade (MBG) were calculated. Patients were followed up for 6 months. Major adverse cardiac events (MACE) were also measured.

RESULTSThere was no significant difference in the baseline characteristics between the two groups. The cTFC parameter in Group A was significantly lower than Group B (18.06 ± 2.06 vs. 25.31 ± 2.59, P < 0.01). The ratio of final MBG grade-3 was significantly higher (P < 0.05) in Group A (87.9%) relative to Group B (65.7%). There was no significant difference between the two groups in final TIMI-3 flow and no-reflow. Patients were followed up for 6 months, and the occurrence of MACE in Group A was significantly lower than that in Group B (6.1% vs. 25.9% respectively, P < 0.05).

CONCLUSIONSMyocardial microcirculation of reperfusion injury in patients with STEMI, after primary PCI, can be improved by administering Lipo-PGE1.

Administration, Intravenous ; Aged ; Alprostadil ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Microcirculation ; drug effects ; Middle Aged ; Myocardial Infarction ; drug therapy ; Percutaneous Coronary Intervention ; methods