In order to obtain the phase I clinical trial data safely and accurately , the subjects management is very important .The purpose of this paper is to introduce the subjects management model during recruitment , screening and observation and discuss the phase I subjects management strategy , according to the author ’ s practical experience and the working model of phase I clinical trials in hospital .

Objective To analyze the monitoring results of urinary iodine of students aged 8 - 10 in Zhangjiakou city,problems in monitoring results,and to provide basic information for working out control strategies of iodine deficiency disorders.Methods A township(town,street) in each country of each city(district) in Zhangjiakou was selected according to 5 positions of the east,the west,the south,the north and center,and 1 village elementary school was sampled in each chosen township,twenty students(half male and female) aged 8 - 10 were selected to collect their urine samples in each school.Urinary iodine concentration was determined by arseniccerium method.Results The median of urinary iodine of the 1700 children aged 8 - 10 was 291.5 μg/L,with ＜ 50 μg/L accounted for 0.8％(13/1700),50 ～ 99 μg/L about 4.9％(83/1700),100 - 199 μg/L about 20.5％ (349/1700),200 - 299 μg/L about 29.7％(504/1700),and ≥300 μg/L about 44.9％(764/1700).Conclusions Urinary iodine has reached the elimination standard of iodine deficiency disorders in Zhangjiakou city.But the situation of more than adequate amount of urinary iodine and iodine excess is relatively serious and it is necessary to lower iodine concentration.

Objective To analyze comprehensively the monitoring data of iodized salt in Zhangjiakou city during 2001 to 2009, and to provide basic information for working out control strategies of the iodine deficiency disorders. Methods According to the iodized salt monitoring requirements in National Iodine Deficiency Disorders Monitoring Program of Ministry of Health, a batch of nine salt samples were taken from each processing (wholesale)company of each county or district of the seventeen counties(districts) of Zhangjiakou once a month. Two townships (towns, street offices) were selected by their location of east, south, west and north in each county(district), and a township in central area each year. Four villages(neighborhoods) were selected in each township(town, street office),and eight household salt samples were collected in each village(neighborhood), and quantitatively determined by direct titration of iodine. Results Iodized salt processing(wholesale) : during 2001 to 2009, a total of 1728 batches was monitored, 1689 batch qualified, batch qualification rate 97.74%;15552 salt samples were tested, 15 357 qualified, iodized salt qualification rate 98.75 %. Household salt levels : 5297 villages (neighborhoods) of 1305 townships(towns, street offices) were monitored, 44 316 salt samples were collected, 43 274 qualified, iodized salt qualification rate 98.04%(43 274/44 141 ), iodized salt coverage rate 99.61%(44 141/44 316), qualified iodized salt consumption rate 97.65%(43 274/44 316). Rate of non-iodized salt was 0.40%(260/44 316), and salt median iodine was 30.02 mg/kg. Conclusions The iodized salt quality indicators are within the state-controlled range in Zhangjiakou city for nine years which remaines at relatively stable levels with a smaller range of annual fluctuations.Detection of non-iodized salt over the years has become the main factors affecting the effectiveness of the prevention and control measures.We should increase monitoring,supervision,and universal health education,and prevent the spread of non-iodized salt.

Methods: A cross-sectional study was conducted based on the data cohort of China multicenter collaborative study of cardiovascular epidemiology in 2007-2008. A total of 7227 participants were enrolled including 3304 male and 3923 female at the mean age of (55.6±7.1) years. Tea drinking information was collected by questionnaire; participants were stratified by gender and grouped by regular tea drinking. Relationship between tea drinking and blood lipids, lipoprotein levels were assessed by covariance analysis. Results: There were 3012/7227 (41.7%) participants (male: 58.9% and female: 27.2%) regularly drunk tea. With adjusted age, urban and rural, education level, cigarette smoking, alcohol drinking, body mass index (BMI), daily red meat intake, physical work intensity, exercise intensity, histories of hypertension, diabetes and hypercholesterolemia, in male gender, compared with non-regular tea drinker, regular tea drinker had decreased blood level of low density lipoprotein cholesterol (LDL-C), the difference was -0.12 mmol/L, P=0.0001 and increased triglyceride (TG), the difference was 0.11 mmol/L, P=0.0001; in female gender, regular tea drinker showed increased high density lipoprotein cholesterol (HDL-C), the difference was 0.06 mmol/L, P<0.0001. Conclusion: In our research, regular tea drinking was negatively related to blood LDL-C level and positively related to TG in male gender, while it was positively related to HDL-C in female gender; the above correlations were independent from possible influencing factors. The impact of long term regular tea drinking on blood lipids and lipoprotein levels should be further prospectively investigated in community based middle and aged population.

Objective To study the pharmacokinetics and safety in healthy volunteers following intravenous administration of biapenem.Methods Ten healthy volunteers were randomized to administer a single dose of biapenem at 300 and 600 mg,respectively.They were given the other dose after a week.The concentration of biapenem in human plasma and urine were determined by HPLC-UV.The main pharmacokinetic parameters were calculated with WinNonLin.Results The main pharmacokinetic parameters of biapenem after single doses of 300 and 600 mg were as follows C_(max) were(11.33±2.71)and(26.80±5.11)μg·mL~(-1);AUC_(0-tn) were(18.01±4.66)and(42.78±8.81)μg·mL~(-1)·h,respectively.Conclusion The process of biapenem in the dosage range of 300-600 mg fit linear dynamic feature.

OBJECTIVETo observe the effect of periodontal initial therapy together with Chinese herbal compound for clearing heat and detoxification (Abbr. TCM) on the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in gingival crevicular fluid (GCF) of patients with chronic periodontitis (CPD).

METHODSThirty-four teeth of 24 patients with CPD were randomly assigned to the control group (17 teeth of 11 patients) and the treated group (17 teeth of 13 patients), they were treated for 8 weeks with periodontal initial therapy, but TCM was given additionally to the treated group. The GCF of the observed teeth was collected at the time before initial therapy (datum line) and at 2 and 8 weeks after treatment. At the same time, the clinical parameters, including probing depth (PD), clinical attachment loss (CAL), and bleeding on probing (BOP) were recorded, and the levels of TNF-alpha and IL-1 beta in GCF were measured by radioimmunoassay.

RESULTSThe levels of TNF-alpha and IL-1 beta in GCF after treatment were significantly lowered in all patients as compared with those before treatment (P<0.01), while PD, CAL and BOP showed significant reduction (P<0.01). After treatment, TNF-alpha and IL-1 beta levels in the treated group were lower than those in the control group (TNF-alpha: 2.5551 +/- 1.0157 microg/L vs 3.4341 +/- 1.0762 microg/L, IL-1 beta: 0.1335 +/- 0.0216 microg/L vs 0.1471 +/- 0.0169 microg/L; P<0.05).

CONCLUSIONTCM could enhance the effect of periodontal initial therapy in lowering TNF-alpha and IL-1 beta levels, which was attributed to reducing the inflammatory reaction of periodontal tissues.

Adult ; Chronic Periodontitis ; metabolism ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Gingival Crevicular Fluid ; metabolism ; Humans ; Interleukin-1beta ; metabolism ; Male ; Middle Aged ; Phytotherapy ; Tumor Necrosis Factor-alpha ; metabolism

Objective The present study was to differentiate the hyperdensities on CT immediately after intra-arterial thrombolysis in patients with acute isehemic stroke.Methods Twenty two patients with acute ischemic stroke were treated with intra-arterial combining with intravenous thrombolysis within 6 hours after onset.All patients underwent nonenhaneed CT scans before,immediately and 24 hours after thrombolytic therapy.The hyperdensities on CT after intra-arterial thrombolysis were analyzed retrospectively.Results Five hyperdense areas were seen in 22 patients immediately after thrombolytie therapy.According to their locations, CT values and follow-up CT scans,the hyperdensities on CT imaging were classified into two groups:contrast enhancement and hemorrhagic transformation.The former was characterized by rapid clearance of the hyperdensity lesion with maximum Hounsifild Unit＜90,on the contrary,the latter was noted by persistence of hyperdensity lesion after 24 hours CT scan with maximum Hounsifild Unit＞90.Two of the five hyperdense lesion patients were confirmed to be contrast enhancement with location in cerebral cortex,the other were hemorrhagic transformation,mostly located in basal ganglia.Hyperdensity in patients with contrast enhancement showed neurological improvement although no further medical cares were offered.Conclusions Different kind of hyperdensity on CT immediately after intra-arterial thrombolysis in patients with acute ischemic stroke can be differentiated according to its location,CT value and follow-up CT scan.When contrast enhancement occurred,no further medical care is needed.

BACKGROUNDChemokines and their receptors have been a research focus in transplantation immunology. Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4(+) T cells in CBA/JxDBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy.

METHODSThe mouse model of spontaneous abortion (CBA/JxDBA/2) and the normal pregnant mouse model (CBA/JxBALB/c) were used. CBA/JxDBA/2 mice were injected with IL-4 (CBA/JxDBA/2-IL-4), IL-4 and IL-10 (CBA/JxDBA/2-IL-4+IL-10), or normal saline (CBA/JxDBA/2-NS) as a control. The expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined.

RESULTSThe embryo resorption rate in the CBA/JxDBA/2 group without any treatment was significantly higher than that in the CBA/JxBALB/c group (17.9% vs 3.7%, P < 0.01). The embryo resorption rate in the CBA/JxDBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4(+) T cells in the CBA/JxDBA/2 group without any treatment was significantly lower than that in the CBA/JxBALB/c group (0.3738 +/- 0.3575 vs 1.2190 +/- 0.2772, P < 0.01); both CCR5 (3.0900 +/- 1.5603 vs 1.2390 +/- 0.6361, P < 0.01) and CXCR3 (2.4715 +/- 0.9074 vs 0.9200 +/- 0.5585, P < 0.01) expressions on CD4(+) T cells of the CBA/JxDBA/2 group without any treatment were significantly higher than those of the CBA/JxBALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/JxDBA/2 group treated with IL-4 (CCR3: 2.0360 +/- 0.6944, CXCR3: 1.3510 +/- 0.5263, P < 0.01) or IL-4 and IL-10 (CCR3: 1.8160 +/- 1.0947, CXCR3:1.0940 +/- 0.7168, P < 0.01). Because of the CCR5, IL-4 and IL-10 (1.9400 +/- 0.8504 vs 3.0900 +/- 1.5603, P < 0.05), but IL-4 alone (2.5310 +/- 1.3595 vs 3.0900 +/- 1.5603, P > 0.05) treatment significantly decreased the expression of CCR5 in CBA/JxDBA/2.

CONCLUSIONSThe abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion. The pregnancy immune tolerance may be induced through selective induction of CCR3, CCR5 and CXCR3 expressions by IL-4 together with IL-10.

Animals ; CD4-Positive T-Lymphocytes ; drug effects ; metabolism ; Cells, Cultured ; Embryo Loss ; metabolism ; Embryo, Mammalian ; Female ; Interleukin-10 ; pharmacology ; Interleukin-4 ; pharmacology ; Mice ; Mice, Inbred BALB C ; Pregnancy ; Receptors, CCR3 ; metabolism ; Receptors, CCR5 ; metabolism ; Receptors, CXCR3 ; metabolism

Adolescent ; Adult ; Antigens, CD ; metabolism ; Antigens, CD1 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Histiocytosis, Langerhans-Cell ; drug therapy ; metabolism ; pathology ; surgery ; Humans ; Infant ; Lectins, C-Type ; metabolism ; Male ; Mannose-Binding Lectins ; metabolism ; Middle Aged ; S100 Proteins ; metabolism ; Survival Rate ; Young Adult

BACKGROUNDThe auditory brainstem implants (ABIs) have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients. The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device. This study aimed to establish an animal model of ABI in adult rhesus macaque monkey (Macaca mulatta).

METHODSSix adult rhesus macaque monkeys (M. mulatta) were included. Under general anesthesia, a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid (RS) approach. The electrical auditory brainstem response (EABR) waves were tested to ensure the optimal implant site. After the operation, the EABR and computed tomography (CT) were used to test and verify the effectiveness via electrophysiology and anatomy, respectively. The subjects underwent behavioral observation for 6 months, and the postoperative EABR was tested every two weeks from the 1 st month after implant surgery.

RESULTThe implant surgery lasted an average of 5.2 h, and no monkey died or sacrificed. The averaged latencies of peaks I, II and IV were 1.27, 2.34 and 3.98 ms, respectively in the ABR. One-peak EABR wave was elicited in the operation, and one- or two-peak waves were elicited during the postoperative period. The EABR wave latencies appeared to be constant under different stimulus intensities; however, the amplitudes increased as the stimulus increased within a certain scope.

CONCLUSIONSIt is feasible and safe to implant ABIs in rhesus macaque monkeys (M. mulatta) through a modified suboccipital RS approach, and EABR and CT are valid tools for animal model establishment. In addition, this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.

Animals ; Auditory Brain Stem Implants ; Deafness ; surgery ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Female ; Macaca mulatta ; Male