To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.

To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.
Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Immunoglobulin M ; blood ; Liposomes ; administration & dosage ; blood ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Mitoxantrone ; administration & dosage ; blood ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

OBJECTIVETo study DNA damage, Bcl-2 and Bax expression, and ultrastructure change in spermatogenic cell of mice by cadmium exposure.

METHODSTwenty-four male mice were divided into 4 groups: 3 groups treated with cadmium chloride of 1, 5, 10 micromol x kg(-1) x d(-1) i.p. respectively for 5 days, and one normal saline control group. The DNA damage of spermatogenic cell by single-cell gel electrophoresis technology was detected. The expression positive rate of Bcl-2, Bax protein in spermatogenic cell by the immunohistochemical method was assayed, and the ultrastructural change of spermatogenic cell by the transmission electron microscope was observed.

RESULTSDNA damage rates of of spermatogenic cell in 1, 5, 10 micromol/kg cadmium chloride groups were higher than that of normal group (P < 0.001). Bcl-2 protein expression positive rates were lower than that of normal group (P < 0.001). Bax protein positive expression rate in 5 micromol/kg group was higher than those in normal group, and 1, 10 micromol/kg groups. The ultrastructure of karyotis, karyotheca, mitochondria, endoplasmic reticulum in three treated groups had different degree of damage and the degree of ultrastructural change was increasing with rising concentration of cadmium.

CONCLUSIONCadmium exposure will cause the DNA break, Bcl-2 and Bax protein abnormal expression and ultrastructural change in spermatogenic cell.

Animals ; Apoptosis ; Cadmium Chloride ; toxicity ; DNA Damage ; Male ; Mice ; Mice, Inbred ICR ; Proto-Oncogene Proteins ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; Spermatozoa ; drug effects ; metabolism ; ultrastructure ; bcl-2-Associated X Protein ; metabolism

Objective To evaluate the setup errors of image guided radiation therapy (IGRT) for head-and-neck cancer using kilovoltage cone beam CT( kV CBCT).Methods 256 patients with head-and-neck cancer were treated with intensity modulated radiation therapy (IMRT) from March 2009 to October 2011.All patients were immobilized with head-and-neck mask and localized with final isocenter marking method using the Philips PQS CT or Philips Brilliance CT Big Bore scanners,which were equipped with LAP movable laser systems.The CT images were transferred to a Varian Eclipse V8.6 workstation for contouring and planning.A kV cone-beam CT scans was acquired,and registered before the treatment for every patient on a Varian iX linear accelerator via OBI system.The setup errors in the right-left ( RL),superior-inferior (SI),and anterior-posterior (AP) directions were recorded.Results The setup errors for the 473 datasets followed a Gaussian distribution.The systematic errors ± random errors in the RL,SI and AP were(-0.6 ± 1.3 ),(0.5 ± 1.6) and (0.9 ± 1.7 ) mm,respectively.The planning target volume (PTV) margins were calculated respectively as 2.4,2.4 and 3.4 mm according to the formula of M =2.5∑ +0.7δ The margins of 288 sets of data using the Big Bore CT scanner were calculated as 2.0,2.1 and 1.7 mm,respectively.Conclusions The setup errors using final isocenter marking method are smaller than those using reference point marking method.The result derived from this retrospective study could be used to set the margin between CTV and PTV.

Objective:To determine the training direction, training program and to promote management of endoscopy nurses by understanding the role delineations and professional practice competencies of gastrointestinal endoscopy nurses in China through a questionnaire survey.Methods:A questionnaire of " role delineations and professional practice competencies for gastrointestinal endoscopy nurses in China" was designed, based on the overseas profile or standards of role delineations and the professional practice competencies. Cross-cultural factors were taken into consideration for a higher content validity, and comments from endoscopic experts were consulted. Questionnaires were sent to participants from 52 medical institutions in 30 provinces, autonomous regions, municipalities.Results:A total of 252 respondents returned questionnaires, whom from 47 medical institutions in 28 provinces, autonomous regions, municipalities. The respondents included 144 endoscopy nurses, aged 35.87±7.43, 53.5% with a junior professional title and 68.8% with a bachelor degree; 65 endoscopy physicians, aged 39.66±5.62, 46.2% with a junior professional title and 40.0% with a doctoral degree; 43 endoscopic-nurse managers, aged 43.12±5.78, 46.5% with a senior professional title and 90.7% with a bachelor degree. The mean score of respondents of the consistency of 12 role delineations and 10 professional practice competencies was over 3.5. The role delineations with the highest score of consistency were " technical assistance" (4.58±0.57), " hygiene and infection control" (4.54±0.62) and " care of endoscopic equipment" (4.47±0.65). The three future role delineations with the highest scores were " hygiene and infection control" (4.58±0.55), " technical assistance " (4.52± 0.62), and " health safety" (4.52±0.58). There was no significant difference in the scores among endoscopy nurses, endoscopy physicians and endoscopic-nurse managers of the consistency of 12 role delineations ( P>0.05). The most consistent professional practice competencies were " cooperation" (4.32±0.61) and " communication" (4.25±0.63), which were also the required professional practice competencies for future development (4.48±0.58, 4.46±0.58, respectively). There was a significant defference between the coincidence on status and the recognition on development of " evidence-based practice and research" competency (3.80±0.77 VS 4.20±0.73, P<0.001). There was no significant difference in the scores of 10 professional practice competencies for future development among endoscopy nurses, endoscopy physicians and endoscopic-nurse managers( P>0.05). Conclusion:There is a consensus among endoscopy nurses, endoscopy physicians and endoscopic chief-nurse managers on the status of the role delineations and the professional practice competencies, as those for future development of gastrointestinal endoscopy nurses in China. " Cooperation" and " communication" are two professional practice competencies that are acknowledged by all types of participants." Evidence-based practice and research" is the professional practice competencies that all the respondents believe that endoscopy nurses need to develop in the future.

Objective To explore the relationship between -262C/T and -21A/T polymorphisms of catalase(CAT) gene and coal-burning borne fluorosis. Methods In 2007, 150 villagers were taken as a nonintervention group in Bijie city from the village of coal-burning borne fluorosis areas with unchanged cooking stoves;150 villagers were taken as the intervention group from the town of Changchun county where cooking stoves changed; 150 villagers were taken as control from non-endemic fluorosis areas in Baiyun town of Changshun county.PCR-restriction fragment length polymorphism were employed to detect genotypes of CAT-262C/T and CAT-21A/T polymorphism of CAT gene. Results The genotypic frequencies of CAT-262C/T and CAT-21A/T in nonintervention group,intervention group and control group were in line with Hardy-Weinberg equilibrium law (P＞ 0.05 ).The genotypes of CC and CT were detected while no TT were detected for CAT-262C/T polymorphism; the genotypes of AA, AT and TT were detected for CAT-21A/T. The genotype frequencies of CAT-262 CC, CT in control group, intervention group and non-intervention group were (89.33%(134/150), 10.67%(16/150); 88.67%(133/150), 11.33% (17/150),93.33% (140/150),6.67% (10/150), respectively. The gene frequency of C in control group, intervention group and non-intervention group were (94.67% (284/300), 94.33% (283/300),96.67%(290/300), respectively. The gene frequency of T in control group, intervention group and non-intervention group were 5.33%(16/300), 5.67%(17/300), 3.33%(10/300), respectively. The genotype frequencies of CAT-21 AA,AT and TT in control group, intervention group and non-intervention group were 48.67%(73/150),46.00%(69/150),5.33%(8/150) ,52.67%(79/150) ,38.00%(57/150) ,9.33% (14/150) ,51.33%(77/150) ,38.00%(57/150), 10.67%(16/150), respectively. The gene frequency of A in control group, intervention group and non-intervention group were 71.67%(215/300),71.67%(215/300),70.33%(211/300), respectively. The gene frequency of T in control group, intervention group and non-intervention group were 28.33% (85/300),28.33% (85/300),29.67% (89/300),respectively. CAT-262C/T and CAT-21A/T genotype and allele frequencies in the control group, the intervention group and non-intervention group showed no significant differences in the distribution(x2= 0.331,0.336, all P ＞0.05 ). Conclusion CAT-262C/T and CAT-21A/T polymorphism is not associated with coal-burning borne fluorosis.

Objective To investigate the association of IL-10 gene promoter polymorphism with susceptibility to hepatitis B viral infection in Han, Yi and Yao ethnic groups from Guizhou province.Methods Five hundred volunteers from Guizhou province were selected to undertake PCR-RFLP for detection of IL-10 gene promoter -592 polymorphisim. Results The genotypic distributions of IL-10-592 were 32.53%- 51.43% (AA),40.74%-54.82% (AC),5.79%-18.52% (CC) whereas the allelic frequencies were 59.94% -72.38% for the A allele, and 27.62%-40.06% for the C allele in Han, Yi and Yao ethnics from Guizhou. The distributions of allele and genotype frequencies of IL-10-592 were statistically different between Yao ethnic in Libo and Yi ethnic in Qianxi, Yao ethnic in Libo and Han ethnic in Libo, Yi ethnic in Qianxi and Yi ethnic in Weining, Yi ethnic in Weining and Han ethnic in Libo (P ＜0.05). IL-10-592 polymorphism was associated with HBV infection in Yi ethnic in Qianxi and the whole population. Conclusion IL-10-592 gene polymorphisms influenced the susceptibility to HBV infection in Han, Yao, Yi sub-populations in Guizhou. Result of the study suggested that IL-10-592 gene polymorphisms might serve as a risk factor to HBV infection.

Phenolic compounds have multiple bioactivities, such as anti-oxidant, anti-tumor, anti-bacterial, and anti-inflammatory activities. Recent literatures have demonstrated that flavonoids have a significant anti-anxiety effect on the central nervous system. In addition, studies showed that flavonoids acted as pro-drugs, which were transformed into smaller phenols through intestinal microflora. The small phenolic metabolites were crucial for the anxiolytic effects of these flavonoids, indicating that natural small-molecule phenols(NSMP) generally have anxiolytic activities. In this paper, the supporting evidences (before June 2016) from SciFinder database have been summarized. Furthermore, NSMPs were classified according to chemical structures; their anxiolytic effects, mechanisms, and the structure-activity relationships were also discussed.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.