Xenograft mice are preclinical animal models of tumors and are widely utilized in anti-tumor research. PK/PD modeling of anti-tumor agents is an approach that can capture the time profile of the "dose-plasma concentration-biomarker level-tumor volume" process based on experimental data from xenograft mice using a non-linear mixed-effect model. PK/PD modeling can help optimize the dosing regimen for anti-tumor therapy, evaluate any synergistic effect and help identify an optimal schedule for combination therapy, as well as providing a preliminary estimate of a drug's efficacy and anti-tumor potency in the human body. PK/PD modeling can also help by quantitatively explaining the mechanism of the tumor-inhibitory effect as indicated by changes in biomarker levels after a drug acts on its target. This article provides a systematic summary of the background, application range, and limitations of the mainstream anti-tumor agent PK/PD models. Recent advances in model structure development are reviewed in detail. Finally, we discuss promising applications of PK/PD models in anti-tumor medicine development from the perspective of a drug's mechanism of action, optimization of combination therapy schedules, and their clinical translation.

Objective To understand brucellosis infective status of Shapotou District, Zhongwei City of Ningxia. Methods The methods of stratified random sampling of epidemiological survey were used among high risk groups in 2008, who underwent erythromycin red plate cohesion test(RBDT) and test-tube agglutination test (SAT), in accordance with the diagnostic criteria for confirming cases of brucellosis(GB 15988-1995). Results Totally an occupational group of 2480 brucellosis in 10 townships were investigated, and 604 sera were tested. Tweenty eight cases were infected, the infective rate was 4.64%(28/604), 15 cases were diagnosed as brucellosis patients, prevalence rate was 2.48% (15/604); cattle attendants had the highest infection rate of 6.45% (26/403). Conclusions Brucellosis epidemic in Shapotou District, Zhongwei City of Ningxia, and it is place related to vocation.

Objective To study the effects of HIF-1α expression on the growth of subcutaneously implanted human hepatocellular carcinoma (HCC) cell lines in nude mice. Methods A nude mouse model of subcutaneously implanted HCC cell line HepG2Tet-on-HIF-1α was established. This cell lines characterizes the inducible expression of HIF-1α by doxycycline (Dos). The impact of HIF-1α expression induced by Dox on the growth of subcutaneously implanted HCC cell lines in the nude mouse model was observed. Results The mRNA and protein expression of HIF-1α were significantly up-regulated in the nude mouse model by oral administration of Dox. Compared with that model in which Dox was not administrated ie Dos( - ) group, the tumor volume(513.545 ± 276. 229) mm3 vs. ( 166. 506 ± 110. 142) mm3 ( P < 0. 05 ), tumor weight ( 1.251 ± 0. 438 ) g vs. (0. 640 ± 0. 296) g ( P < 0. 05 ), and tumor growth velocity were significantly enhanced in Dox ( + ) group, while tumor necrosis was inhibited ( 31. 360% ±2. 728% vs. 36. 640% ± 3. 804% ) (P<0. 05). The weight loss of nude mice was larger in Dox( + )group( P < 0. 01 ). There was no liver or lung metastasis in either group. Conclusion The expression of HIF-1αin subcutaneously implanted HCC in a nude mouse model is up-regulated by oral Dox. High grade expression of HIF-1α promotes the growth of implanted HCC.

Objective To study metabolism of polyunsantured fatty acid (PUFA) and to investigate the relationship between different PUFA compositions and △6 desaturase (D6D) activity in colorectal carcinoma (CRC).Methods Fresh frozen malignant CRC tissues were obtained from 61 patients and blood samples were detected in 38 patients.The PUFA composition in these samples was determined by gas-liquid chromatography on a capillary column.The fatty acid product-to-precursor ratios in blood and tissue as estimates of desaturase activity (D6D activity index),and its relationship with the ratios between different PUFA compositions were investigated.Results Metabolism of ω-6 PUFA dominated in PUFA metabolism path.The ratio of ω-6/ω-3 PUFA was 4.89 in blood samples and 10.15 in tissues.The ratio of LA/ALA was 101.92 in blood samples and 86.16 in tissues.The ratio of ω-6/ω-3 LC-PUFA was 2.86 in blood samples and 4.51 in tissues.The D6D activity index in ω-6 PUFA metabolic processes both in tissues (t =1 1.609,P =0.00) and blood samples (t =-9.151,P =0.00) were higher than that in ω-3 PUFA.Conclusion In colorectal carcinoma,the ω-6 PUFA metabolic not only plays an important role in the metabolism of PUFA,but also is more active than the ω-3 PUFA metabolic,and in some way links to the development of tumorigenesis in CRC.

Objective To discuss the technique and value of preoperative reformatting with three-dimensional computed tomography technique for C_2 pedicle screw track.Methods GE Light Speed 16 Pro spinal CT scans of 15 adult dry vertebrae were loaded into an imaging station (software ADW4.2).Two methods of C_2 pedicle screw techniques were analyzed through virtual screw trajectory by VR (volume rendering) and MPR (multiple planar reformatting) techniques,in method A,screw entry point was the intersection between the media-vertical and the cranial line of C_2 inferior facet joint,in method B,the screw track was from the cranial and medial quadrant of the dorsal part of C_2 inferior facet joint.Results The screw track could be observed dynamically from any plane.Two vertebrae were ob- served with smaller height in isthmus and the medial edge of the transverse foramen since no space was a- vailable for the screw.The screw trajectories data were compared between method A and method B,which showed that the angles towards the cephalad (in sagittal plane) and midline (in transverse plane) were bigger in method A than in method B (P＜0.05,0.01),but the safe screw diameter was smaller in method A than in method B (P＜0.05),and there was no difference of the screw length between the two methods(P＜0.05 ).Conclusion In this research,the individual C_2 pedicle screw entry points, screw diameter and security screw angle can be simulated,and the screw track can be observed dynami- cally to make sure if it transits the bone structure completely.Preoperative three-dimensional computed tomography reformatting for pedicle screw track is of great value in clinical and basic researches.

OBJECTIVETo explore the relationship between the CT findings of steatohepatitis and the special environmental factors in highland area, such as anoxia and life styles.

METHODSCT scan was performed for 64 patients, who were 44 males and 20 females in Tibet with a 3500-meter elevation.

RESULTSHypodensity in liver parenchyma and the invertion of liver density and spleen density were found in all the 64 patients. According to the degree and scope in their pathological changes, these patients were divided into three groups: severe 14, moderate 26, and mild 24.And diffused 43, sectional 14, regional 7 by CT findings. Among the 44 drinkers, 34 with more than 10 years were diffused by CT scan, the other 10 drinkers under 10 years, diffused 8, and sectional 2. In addition, the 27 steatohepatitis patients were all diffused by CT who were obese and had drinked more than 10 years.

CONCLUSIONanoxia and drinking excessively in highland area are relevant to fatty degeneration in liver.

Adult ; Aged ; Altitude ; Fatty Liver ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed

Objective To study the changes and significance of serum beta 2-microglobulin(?2-MG),cytocine interleukin-2(IL-2) in the clinical progress of childhood idiopathic thrombocytopenic purpura(ITP).Methods One hundred and ten patients of childhood ITP were chosen for the test group(70 cases of primary ITP and 40 cases of recurrent ITP),and 110 normal children for the control group.Levels of serum ?2-MG and IL-2 were determined by radioimmunoassay kit and analysed with two sample t-test.Results Among the patients,the serum IL-2 levels were significantly lower and serum ?2-MG levels were significantly higher than those in control group(P0.05).Conclusion Determining serum IL-2 and ?2-MG levels has important significance to reflect the progress of disease and direct treatment.

Objective To characterize the vascular cognitive impairment of stroke patients with different injury sites (right or left cerebral hemisphere) and pathological type (hemorrhage or infarct). Methods A total of 119 stroke patients were assessed with regard to their cognitive functions using the LOTCA within one week of admis-sion, and comparison was made among patients in terms of VCI characteristics, injury site, and pathological type. Results In patients with left hemisphere injury, there found no significant difference between those with cerebral in-farct and hemorrhage with regard to the total score of LOTCA, but the score of perception of those with hemorrhage was lower than those with infarct(P<0.05). in patients with right hemisphere injury, both total score of LOTCA and the subscore were not significantly different between those with infarct and hemorrhage(P>0.05). In patients with infarct in left hemisphere, the total score of LOTCA was lower than those with infarct in right hemisphere(P<0.05), but the scores of orientation and thinking operation were lower than those with infarct in right hemisphere(P<0.001 or <0.01). In patients with hemorrhage in the left hemisphere, the total score of LOTCA was not significantly different from those with hemorrhage in right hemisphere, but the scores of orientation and perception were lower than thosewith hemorrhage in right hemisphere(P<0.001 or <0.01). Conclusions More attention with regard to perception training should be paid to those with cerebral hemmorhage than those with cerebral infarct. In patients with cerebral infarct, more attention with regard to orientation and thinking operation training should be paid to those with infarct in left side, while for those with cerebral hemorrhage, more attention with regard to orientation and perception training should be paid to the left hemisphere insult.

Objective To study the value of using endoscopy iodine staining combined detecting the expression of p53, survivin and telomerase in the diagnosis of early esophageal carcinoma and precancerous lesions. Methods Three hundred patients who received routine gastrescopy and had high risk of esophageal carcinoma were examined by the iodine dyeing on their esophageal mucosa with 2. 5% Lugol solu-tion. Multiple biopsies were taken from the unstained or light-stained areas when their diameters were over 5mm for pathology diagnosis. The expression of p53, survivin and telomerase were detected by immunohistochemical staining. Results With the Lugol staining method, the incidences of light, moderate and high grade dysplasia and early esophageal carcinoma were 16. 3% ,9. 7% ,3.7% and 4. 3% respectively. The expression of p53, survivin and telomerase were related and the unstained were related to the expression of p53, survivin and telomerase in dysplasia and early esophageal carcinoma. Using endoscopy iodine staining combined testing p53, survivin and telomerase showed sensitiv-ity of 100%, specificity of 92. 3% and accuracy of 91.8% to diagnose of early esophageal carcinoma and high grade dysplasia. Conclusion Lugol solution chromoendscopy combined assay of p53, survivin and telomersse might be useful in the diagnosing early esophageal carcino-ma and precancerous lesion.

Objective Attenuated strains of Shigella are attractive live vaccine candidates for eliciting mucosal immune responses which is a suitable carrier for the prophylactic human papillomaviruses (HPV) vaccine development, To examine the potential of a live Shigella based prophylactic HPV vaccine, HPV16L1should be expressed in attenuated shigella strain. Methods A Shigella large invasive plasmid (icsA/virG) based prokaryotic expression plasmid pHS3199 was constructed. HPV16L1 gene was inserted into plasmid pHS3199 to form pHS3199-HPV16 L1 construct, and pHS3199-hpv16L1 was electroporated into a live attenuated shigella strain sh42. The expression of HPV16L1 protein was demonstrated by Western blotting with monoclonal antibody to HPV16L1, The genetic stability of recombinant strain sh42-HPV16 L1 was monitored by consecutive passage culture. Invasive ability of sh42-HPV16L1 was evaluated by Hela cell infection assay. Results HPV16 L1 protein can be expressed in recombinant strain sh42-HPV16 L1, and the protein stably expressed over 140 generations. The invasive ability of sh42-HPV16L1 was diminished dramatically compared to its parent strain, but not abolished completely. Conclusion HPV16L1 protein was constitutively expressed in the attenuated strain of shigella flexneri sh42, and maintained partial invasive ability. Our strategy may represent a promising vaccine candidate against genital HPV16 infection.