Objective To analyze the epidemiological characteristics of human brucellosis in Harbin City.Methods Retrospective study was used to collect the information of brucellosis epidemic situation and monitoring data.The information of brucellosis cases was from China disease surveillance information system and from the Harbin surveillance results of brucellosis between 2004 and 2013.According to the results of epidemiological characteristics of brucellosis in Harbin,analysis of regional distribution,time distribution,population distribution and brucellosis serology positive rate were conducted in 18 counties (cities,districts) of Harbin.Data were analyzed using SPSS 13.0 software.Results From 2004 to 2013,2 602 cases of brucellosis were reported.In particular,the largest increase was in 2012,a total of 481 cases was reported,which was 2.11 times that of 2011 (228 cases).The incidence was raised from 2.20/100 000 to 5.98/100 000,and the epidemic range expanded from 15 counties (cities,districts) to 18 counties (cities,districts).Age of onset concentrated in young adults,the 20-59 years old group accounting for 86.47％ (2 250/2 602) of the total incidence.The proportion of male and female was 2.90 ∶ 1.00 (1 936 ∶ 666).The occupation of most new cases was farmers,accounting for 83.55％ (2 174/2 602) of the total incidence.In brucellosis surveillance,4 877 people was undergo serological test,the positive number was 145,and the positive rate was 2.97％.Conclusion Human brucellosis epidemic has an increasing trend in Harbin,age of onset is concentrated in young adults,males are more than females,and the epidemic range expands year by year.

Objective:To investigate the relationship of polymorphism of leptin receptor gene Gln223Arg with asthma and metabolic syndrome.Methods: Collected 120 asthma patients,92 metabolic syndrome patients,54 asthma combined metabolic syndrome patients and 81 normal controls.According to the severity,the asthma patients were divided into mild-medium group and severe group.The serum leptin level was measured by ELISA,the genotypes of leptin receptor were analyzed by the method of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),and statistcs of each subject′s MBI,blood pressure,lung function and fasting blood glucose were collected.Results: ①There were significant differences in genotype and allele frequency in leptin receptor gene Gln223Arg between the metabolic syndrome group,asthma combined metabolic syndrome group and normal control group(P<0.05).②The allele frequency and genotype in leptin receptor gene Gln223Arg were significant different between the severe asthma group and normal control group(P<0.05).③The serum leptin level,BMI and systolic blood pressure of AA+AG genotype group were significiant higher than GG genotype group(P<0.05),while the value of FEV1% and FEV1/FVC of lung function were lower than GG genotype group(P<0.05).Conclusion: Leptin receptor gene Gln223Arg polymorphism is correlated with asthma and metabolic syndrome,and by causing leptin resistance,the A allele might be the genetic factor that contribute to individual susceptibility for asthma and metabolic syndrome.

Objective To preliminarily observe the clinical efficacy of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) using helical tomotherapy (HT) in patients with limited-stage small-cell lung cancer (LS-SCLC) after chemoradiotherapy,and compare HT with intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in dose distribution.Methods From April to June,2014,six patients with LS-SCLC who had achieved a complete remission after chemoradiotherapy were assigned to HS-PCI using HT within a month after brain metastasis was ruled out using brain magnetic resonance imaging (MRI).After fusing CT images and MRI images,the hippocampus was contoured in the fusion images and hippocampal avoidance regions were created using a volumetric expansion of 3 mm around the hippocampus.A dose of 25 Gy in 10 fractions to 95％ of planning target volume (PTV) was prescribed in HT,IMRT,and VMAT.The clinical efficacy,adverse reactions,neurocognitive function,and brain metastasis were evaluated for HT.The dose distribution in PTV and hippocampus were compared between HT,IMRT,and VMAT.Results There were one patient with abdominal wall and abdominal lymph node metastases,one patient with local recurrence,and no patient with brain metastasis during the observation period.The numbers of patients with grade 1 and grade 2 headache,dizziness,and hair loss reactions were 3 and 1,3 and 1,and 4 and 2,respectively.There were no significant differences in the average score of the Mini-Mental State Examination before treatment and at 3 and 6 months after treatment (29.7,29.2,and 29.3 ; P =0.083,0.317,and 0.157).The mean dose to the hippocampus was 16.85 Gy for IMRT and 17.59 Gy for VMAT.For HT,the mean doses to the hippocampus and avoidance regions were reduced to 5.26 Gy and 6.21 Gy,respectively.The prescribed dose for HT was reduced by 79％ and 71％ compared with IMRT and VMAT,respectively.The average coverage rate of the prescribed dose was 94.48％ for HT.Conclusions HT achieves promising dose distribution and target coverage in sparing of the hippocampus.Moreover,HT dose not increase the incidence of adverse reactions.The change in neurocognitive function needs to be further studied with longterm observation and large-scale sampling.

Objective To investigate the therapeutic effect of insulin combined with oral hypoglycemic agents on cognitive function of patients with Alzheimer′s disease(AD) and diabetes mellitus(DM).Methods We retrospectively reviewed 135 cases of AD patients with type2 DM(T2DM) admitted to our hospital between March 2011 and March 2013. According to drug use , they were randomly divided into two groups , oral hypoglycemic drug group ( group A, 65 cases ) and insulin combined with oral hypoglycemic drug group (group B,70 cases).After 12 months of follow-up, the Mini Mental State Examination (MMSE) score by Folstein et al and Clinical Global Impression Scale (CGI) were used to assess their cognitive function .Results After 12 months of treatment , the MMSE score decreased significantly in group A ( P=0.000), but not in group B(P=0.281).Also, CGI-C scores showed significant deterioration for all domains after 12 months in group A vs group B(P=0.001).Conclusion Insulin therapy can effectively slow down the decline of cognitive function in patients with AD .

Objective To investgate risk factors of delayed bleeding after endoscopic submucosal dissec-tion(ESD)for early colorectal tumor and precancerrous lesions. Methods We retrospectively reviewed clinical date of 138 patients with early colorectal tumor and precancerrous lesions who received ESD in Hubei Cancer Hos-pital from October 2012 to October 2016. Risk factors of delayed bleeding were analysed by univariate and multi-variable logistic regression analysis. Results Ten(7.2%)of 138 patients occurred delayed bleeding after ESD. Univariate analysis showed that there was significent difference between the bleeding group and the non-bleeding group in location of the lesion(P = 0.022),severe fibrosis of submucosa(P = 0.016),Obvious intraoperative bleeding(P = 0.032)and inadequate endosopic experience of endoscopist(P = 0.045). Multivariate Logistic re-gression analysis showed that location of lesion(P = 0.003,OR = 4.64,95%CI:1.71~12.58),severe fibrosis of submucosa(P = 0.009,OR = 4.83,95% CI:1.49~15.60)were independent risk factors of delayed bleeding after ESD for early colorectal tumor and precancerrous lesions. Conclusion Patients with early colorectal tumor and precancerrous lesions in the rectum and severe fibrosis of submucosa are prone to delayed bleeding after ESD.

Objective To construct oligomeric hyaluronic acid(5 KDa)-modified ellagic acid-loaded liposomes(EA-HA-L)to improve the aqueous solubility,in vitro transdermal effect and whitening activity of ellagic acid.Methods Oligomeric hyaluronic acid-modified cholesterol(HA-Chol)was prepared by esterification reaction and structurally characterized by FTIR and 1H NMR;Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes were prepared by film dispersion-ultrasound method,and the prescribing process was optimized by Box-Behnken design-response surface method,and the particle sizes,the polydispersity index(PDI),zeta potential and encapsulation rate of liposomes under the optimal prescribing process were determined;the difference in solubility between EA-HA-L and free EA was evaluated;in vitro transdermal effect of liposomes were investigated using rat abdominal skin;inhibitory effect on tyrosinase and intracellular tyrosinase in mouse melanoma cells(B16-F10)was surveyed via dopa oxidation method.Results HA-Chol was synthesized and characterized;the optimized prescription process was mass ratio of 10:1 for soy phospholipids to HA-Chol,lipid-drug ratio of 40:1,hydration temperature of 30℃,hydration time of 60 min,ultrasound intensity of 35％,ultrasound time of 21 min,and the particle size of EA-HA-L produced under the optimized prescription process was(140.30±1.30)nm,PDI was(0.29±0.01),the encapsulation rate of ellagic acid was 91.16％±3.06％,and the zeta potential was(-5.67±0.09)mV;after EA was encapsulated by liposomes,the solubility of EA in water increased by about 40-fold;the cumulative transdermal amount of EA-HA-L was 46.98±2.17 μg·cm-2 in 24 h,and the intradermal retention was 66.15±0.61 μg·cm-2,which was 1.72 times higher than that of free EA(P<0.0001)and 1.23 times higher than plain liposome(EA-L)(P<0.01);and the tyrosinase inhibitory activity of EA-HA-L was higher than that of both free EA and EA-L in the EA concentration range of 50-400 μg·mL-1.Conclusion Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes with small particle size and high encapsulation rate were successfully prepared.EA-HA-L significantly improved the water solubility of EA and possessed better transdermal effect and stronger whitening activity than free EA and EA-L.

Objective:To study the protective effects and mechanisms of melatonin (MTn) on lipopolysaccharide (LPS) and hypoxic-ischemic(HI) induced white matter damage (WMD) in neonatal rats.Methods:Seventy-two 3-day-old newborn Sprague-Dawley (SD) rats were randomly assigned into sham operation group (the sham group), model group (the HI group) and MTn intervention group (the HI+MTn group) ( n=24 for each group). For the sham group, only dissection of the right common carotid artery was performed without ligation. Animal models of WMD were established using LPS pretreatment and HI method in both the HI group and HI+MTn group. The HI+MTn group received MTn intraperitoneal injection (15 mg/kg, 1 h before LPS injection and then once daily). The HI group and the sham group received equal volume of normal saline containing 1% ethanol intraperitoneal injection. The rats were sacrificed on d7 of experiment and periventricular white matter (PVWM) was collected for hematoxylin-eosin (HE) and TUNEL staining to determine WMD and apoptosis. The distribution and morphology of microglial cells in the PVWM were studied using IBA1 immunofluorescence staining. Reactive oxygen species (ROS) kit was used to detect ROS. The expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, IL-18 and mitochondrial autophagy markers (pink1 and parkin) were determined using real-time quantitative PCR. Results:Compared with the sham group, the HI group showed WMD, cell degeneration and necrosis,increased cell apoptosis and increased expressions of NLRP3 inflammasomes and downstream inflammatory factors (IL-1β and IL-18) in PVWM. Compared with the HI group,the HI+MTn group showed reduced WMD, cell apoptosis, microglia infiltration and inflammatory factors expression. MTn increased pink1 and parkin expression and reduced ROS production in PVWM.Conclusions:MTn reduces ROS production by enhancing mitochondrial autophagy and inhibits NLRP3 inflammasomes hyperactivation to alleviate endotoxin- and HI-induced WMD in neonatal rats.

Objective: To investigate the relationship between urinary monohydroxylated metabolites of hydroxyl polycyclic aromatic hydrocarbons (OH-PAHs) and lung function, as well as the role of oxidative stress in these associations, so as to provide a scientific basis for air pollution control and policy formulation. Methods: A panel study was carried out among 45 young healthy adults. Four follow up surveys and health examinations were conducted from November 2017 to October 2018 to measure lung function parameters [forced vital capacity (FVC), second forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), FEV1/FVC, and forced expiratory flow between 25% and 75% vital capacity (FEF 25%~75% )], markers of exposure to 7OHPAHs [∑ 7OH PAHs], and markers of oxidative stress[8 hydroxy 2 deoxyguanosine (8 OHdG) and 8 isoprostaglandin F 2α (8 iso PGF 2α )]. The relationship between urinary PAH metabolites and lung function was quantified by linear mixed effects models. Mediation analysis was performed to assess the role of oxidative stress in the relationship between OH PAHs and lung function. Results: The median values of FVC, FEV1, FEVI/FVC, PEF, and FEF 25%-75% were 4.37 L, 3.58 L, 83.00%, 4.38 L/s, and 3.32 L/s, respectively. The results showed that each 1 unit increase in log transformed value of 2 Hydroxyfluorene (2 OHFlu) was associated with a 5.05% decrease ( β %=-5.05%，95% CI =-8.85%--1.09%) in FVC, 4.15% decrease ( β %=-4.15%，95% CI =-7.94%- -0.22% ) in FEV1 and 5.87% decrease ( β %=-5.87%，95% CI =-11.35%--0.05%) in FEF 25%-75% , respectively. Each 1 unit increase in log transformed values of 2 OHFlu and 9 Phenanthrol (9 OHPhe) was associated with a 7.03% decrease ( β %=-7.03%，95% CI =-12.60%--1.11%) and a 7.08% decrease ( β%=-7.08%，95% CI =-13.50%--0.17%) in PEF, respectively. Additionally, urinary ∑ 7OH PAHs had a positive correlation with the levels of urinary 8 OHdG and 8 iso PGF 2α ( r =0.64, 0.69, P <0.01). Meanwhile, the levels of 8 OHdG mediated 17.06% and 15.71% of the association between 2 OHFlu with FVC and FEV1. Conclusion The finding reveales a negative relationship between urinary OH PAHs and lung function among young healthy adults. The 8 OHdG plays a mediated role in the correlation of 2 OHFlu with FVC and FEV1. Active relevant policies are needed to control air pollution and maintain the healthy living conditions of young people.

Objective: To obtain the high-resolution dose distribution for the single source channel of Leksell 4C gamma knife. Methods: A parallel computing platform based on the Message Passing Interface (MPI) and Monte Carlo Code MCNPX was established. The ring-shaped detector and two pre-validated variance reduction techniques (emission direction-biased sampling of source and termination of electron tracking in partial structures) were adopted to derive the high-resolution dose distribution for the single source channel of Leksell 4C gamma knife. The effect of cut-off energy for both photon and electron on the accuracy of simulation outcomes was evaluated and statistically compared. Results: Compared with previous findings, the spatial resolution of the dose distribution for the single source channel obtained in this study was higher (radial resolution=0.1 mm) with less statistical error (<1%). The calculation time was acceptable (approximately 24 h). For the 4-, 8-, 14-and 18-mm variable collimators, the penumbra and full width at the half maximum (FWHM) for single side were 1.0, 1.1, 1.2, 1.3 mm and 2.2, 4.3, 7.3, 9.3 mm, respectively, which were consistent with previous studies. The difference of the simulation results was extremely small between different cut-off energy for photon (1 keV vs.10 keV). However, the simulation results significantly differ between 1 and 521 keV electronic cut-off energy. Conclusions The MCNPX parallel computing platform based on the MPI environment can be utilized to derive highly accurate dose distribution with high resolution in acceptable calculation time. The cut-off energy of the photon and electron should be cautiously set up during simulation.

Objective The IAEA report No.483 describes the latest method of small field dosimetry.The field output factor measurement and correction methods are used to improve the accuracy and consistency of the measurement results for different type detectors.Methods The field output factors from 0.6 cm×0.6 cm to 10 cm× 10 cm were measured using IBA's CC13 ionization chamber,CC01 ionization chamber,PFD semiconductor detector,EFD semiconductor detector and Razor semiconductor detector,respectively.The field output correction factors were used to correct the measurement result.Results Compared with the corrected data,the results of ionization chamber are mainly affected by the volume averaging and the fluence perturbation effect,lead to the measurement result which is 4.70％ lower at 0.6 cm × 0.6 cm;The results of Shielded semiconductors are mainly affected by fluence perturbation effect,lead to the measurement result which is 4.80％ higher at 0.6 cm × 0.6 cm.The results of unshielded semiconductors are mainly affected by energy response and fluence perturbation effect,resulting in lower measurement results at the field size＞0.8 cm×0.8 cm,2.10％ lower at field size of 1.5 cm× 1.5 cm,higher measurement results at field size＜0.8 cm×0.8 cm and 1.1％ higher at field size of 0.6 cm×0.6 cm.Before the correction,the measurement results from different types of detectors are quite different,average standard deviation is 0.016 6.After the correction,the difference among the detectors is significantly reduced,average standard deviation is 0.006 6.Conclusions For detectors such as ionization chambers and semiconductors,the field output correction factors can be used to correct the output factors of the small field to improve the accuracy and consistency of the measurement results.