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 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 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 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.

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 To investigate the ideal dosage of dexmedetomidine( DEX) with 1?0 μg/kg fentanyl for monitored anesthesia care ( MAC) during endoscopic variceal ligation ( EVL) . Methods A total of 60 patients scheduled for elective EVL were randomly divided into 3 groups ( n=20) . After fentanyl was infused intravenously at the dosage of 1?0 μg/kg, the loading dosage of DEX at 1?0 μg/kg ( group D1 ) , 1?5 μg/kg ( group D2 ) , or 2?0μg/kg ( group D3 ) was continuously infused in 10 min, respectively. When the modified OAA/S score reaching≥3 point, EVL was carried out. The change in modified OAA/S score, the operation duration time, recovery time, satisfaction rates of patient and doctor, and complications were recorded. Results There were no significant differences in regarding of general status, operation duration time and satisfaction score of patients between the 3 groups ( P>0?05 ) . Before endoscope insertion, the OAA/S score in group D3(4?4±0?2)was higher than that in D1(3?4±0?5)or D2 groups(3?8±0?3)(P<0?05), and there was no significant difference between the scores of D1 and D2(P>0?05).At the time?point of 5 mins after endoscope insertion, the OAA/S score in group D3(4?5±0?3)was significantly higher than that in D1(3?5±0?6)or D2 groups(3?7±0?4)(P<0?05),there were no significant differences between D1 and D2( P>0?05) . At the end of the procedure,there was no significant difference in OAA/S score between the 3 groups(P>0?05).Compared with group D1(3?1±0?9)min and D2(3?8±0?8)min, the recovery time in group D3(6?6±1?2)min was significantly longer (P<0?05), while there was no significant difference between D1 and D2(P>0?05). The satisfaction score of endoscopist in group D1(8?0±0?8) was significantly lower than that in group D2(9?4±0?6)or D3(9?5±0?5)(P<0?05), there was no significant difference between groups D2 and D3 ( P>0?05 ) . No tachycardia, hypertension or hypoxemia occurred during the procedure. There was no significant difference in rate of hypotension among the three groups ( P>0?05) . The incidences of nausea(30%) and body movement(15%) in group D1 were significantly higher than those in group D2 and D3(P<0?05).There were no differences between D2 and D3(P>0?05). The incidence of bradycardia in group D3(40%) was significantly higher than those in group D1(0) and D2(10%)(P<0?05).There were no differences between those in D1 and D2(P>0?05). Conclusion Combined with 1?0 μg/kg fentanyl, 1?5 μg/kg DEX is more efficient and safer for EVL in the status of MAC.

Objective To reconstruct the Chinese visible human (CVH) dataset with the reconstruction algorithm, the Visualization Toolkit (VTK), and to realize long-distance accessing and alternating operation associated with virtual reality modeling language (VRML) under web condition. Methods 3D structure of the humerus was reconstructed and put out in web condition by applying the methed of capturing data of digitalized visible human. Results The 3D structure of the humerus was successfully reconstructed. These 3D images displayed the anatomical relationships of the structures of the humerus in explore windows with any angle and scale. All reconstructed structures were represented conveniently. Conclusion Based on VTK and VRML, 3D reconstruction of the humerus is realized, which will provide the support and reference for further research on the others structure's visualization of human body, and also for Visualization in Scientific Computing and long-distance teaching in anatomy.

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.

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