OBJECTIVE:To study the influence of calcineurin gene polymorphism on the efficacy of cyclosporine A (CsA). METHODS:The blood samples of patients treated with CsA were collected. The trough blood concentration of CsA was detected by EMIT. The genotype of PPP3CA and PPP3CB was assayed by RFLP-PCR method. The expression of NFAT-regulated gene IL-2, IFN-γand GM-CSF were measured by RT-qPCR,which were used to define the index of indirect efficacy of CsA. The relationship of gene polymorphism with CsA efficacy was study by relationship analysis and multiple factor regression method,etc. RESULTS:A to-tal of 100 blood samples were collected. There was no significant correlation between the expression of CsA efficacy-related NFAT-reg-ulated gene GM-CSF and trough concentration of CsA(rGM-CSF=-0.04,P=0.238);the expression of IL-2 and IFN-γ were negatively correlated with trough concentration of CsA significantly(rIL-2=-0.384 3,P<0.001;rIFN-γ=-0.335 4,P<0.001). Using the average value of mRNA expression of IL-2 and IFN-γas indirect efficacy index,the polymorphism of PPP3CB rs3763679 site significantly in-fluenced the efficacy of CsA(P<0.05),but PPP3CA rs3804358 had no any effect on it(P>0.05). Stratified analysis showed that among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 genovariation(TC+TT) were better than those with wild-type gene (CC)(P<0.05). After the efficacy was normalized by CsA trough concentration, multivariate analysis showed that normalized efficacy of CsA was negatively correlated with gender,PPP3CB rs3763679,lactate dehy-drogenase and creatinine significantly,but positively correlated with PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate,etc. CONCLUSIONS:PPP3CB rs3763679 gene polymorphism influence the efficacy of CsA;among patients with immune disease underwent renal transplantation,efficacy of patients with PPP3CB rs3763679 TT+TC is better than that of CC type. At the same time,gender,PPP3CA rs3804358,leucocyte count,usea nitrogen,glycerin trilaurate and other factors all can influence the nor-malized efficacy of CsA to different extent. Multiple factors should be considered when using CsA.

From August 2007 to January 2009 a total of 95 patients with complex renal calculi were treated with CT ( n = 32 ), X-ray ( n = 33 ) or ultrasound ( n = 30 ) guided percutaneous nephrostomy and ureteroscopic holmium laser lithotripsy respectively. The CT guided procedure had lower positioning time,positioning failure rate, complication rate and residual stone rate than those of X-ray and ultrasound localization, particularly had advantages in the stone clearance rate and complications rate ( all P ＜ 0. 05 ).CT guided localization can be chosen in the following conditions: higher kidney position, large staghorn calculi or renal pelvis stones without hydronephrosis, with congenital renal malformations or failure of ultrasound or X-ray localization.

Abstact:Objective To study the relationship between acute mountain sickness and geographic factors in young males,and provide no-vel materials for screening susceptible population and exploring novel research ideas and methods. Methods Total 294 young men came from low altitude were randomly selected,questionnaire was conducted and military AMS standard was applied for diagnosis. Binary logistic re-gression was used to analyze the relationship between 10 different geographical factors and AMS incidence and figure out the risk factors for medical geographical differences of AMS. Results AMS incidence was 52. 04% (153 people),with most commonly seen dizziness,head-ache,shortness of breath,chest tightness and lip empurples,the occurrence was 89. 54%,84. 31%,66. 01%,65. 36% and 60. 78%,respec-tively. Binary logistic regression analysis revealed that altitude was the only geographical risk factor (OR=0. 998,P<0. 05). Conclusion Among the population who entered plateau,lower native altitude they used to live brings higher risk of AMS,therefore corresponding preven-tions should be adapted for those who come to high altitude from low altitude in order to ensure their health and safety.

ObjectiveTo study serum proteomic fingerprints of colorectal cancer during onset and progression and to screen tumor markers related to prognosis.Methods Serum from colorectal cancer patients, non-cancer patients, and healthy control were profiled using WCX ProteinChip or magnetic beads and analyzed by mass spectrometry. Results Seven protein peaks were found related to colorectal cancer. Several peaks were closely related to lymph node metastasis, distal organ metastasis and decreased after surgery. The diagnostic model composed of 3398.3、5477.1、8453.9 u can detect CEA negative colorectal cancer in 100%. Conclusion Protein fingerprinting technology (PFT) in conjunction with bioinformatics can significantly identify novel biomarkers in the serum of colorectal cancer patients with potential values for prognostic evaluation, detection of CEA negative colorectal cancer and changing its progression.

BACKGROUND:It has been found that central nervous system is involved in Guillain-Barre syndrome and Miller-Fisher syndrome, and the involved sites include optic nerve, brain stem and cerebellum. Abnormal signal of MRI can be observed in the brainstem and spinocerebellar tract of patients with Miller-Fisher syndrome. To establish an animal model of encephalitis after infection of Campylobacter jejuni, and investigate the mechanism of formation by means of imaging, immunology and pathology.OBJECTIVE: To construct an animal model of lesion of central nervous system after infection of Campylobacter jejuni Penner 4.DESIGN: A randomized grouping designed, controlled animal experiment.SETTING: Department of Imaging and Department of Neurology, Second Hospital of Hebei Medical University.MATERIALS: The experiment was carried out in the Laboratory of Molecular Imaging, the Second Hospital of Hebei Medical University between August and December 2003. Fifteen healthy flap-eared rabbits were randomly divided into experimental group (n=10) and control group (n=5).METHODS: In the experimental group, Campylobacter jejuni inactivated bacteria liquor was completely emulsified with complete Freund adjuvant (CFA) of the same volume in week 1, and then the rabbits were immunized with subcutaneous injection at multiple points of bilateral axilla, bilateral groins and side of back spine, 1 mL for each site, and 5 mL for each rabbit; The rabbits were further immunized with intraperitoneal injection of simple Campylobacterjejuni inactivated bacteria liquor in the following every two weeks, 5 mL for each time in each rabbit for 5 times. In the control group, the Campylobacter jejuni inactivated bacteria liquor was replaced by saline of the same volume, the injected method and time were all the same as those in the experimental group. Evaluative methods: ①Symptoms and physical signs: their mental status, conditions of diet, urine and excrement, and activities of limbs were observed; ② Serological examination: the contents of anti-Campylobacterjejuni antibody, anti-IgG GM1 antibody and myelin basic protein (MBP) were detected with enzyme-linked immunoadsorbent assay (ELISA); ③ MRI examination was applied to the randomly selected rabbits before every immunization with Toshiba 1.5 T MRI instrument. The scanning sequence included spin-echo T1-weighted image with the scanning parameter of 500/15 ms (TR/TE); rapid spin-echo T2-weighted image, 4 000/108 ms (TR/TE); fluid attented inversion recovery (Flair) sequence, the parameter was 10 000/120 ms (TR/TE), inversion angle was 90°. The thickness of scanning layer was 4.0 mm, and the layer space was 0.8 mm. ④ Histological examination: At 4 weeks after the first immunization, the attacked animals were induced to death by cardiac perfusion, and the skull was opened immediately to remove optic nerve, part white matter, hippocampus, brainstem, cerebellum and spinal cords of neck, chest and waist, which were fixed with formaldehyde solution (40 g/L),and hematoxylin-eosin (HE) staining, fast blue staining and MBP immunohistochemical staining were performed respectively. At 10 weeks after immunization, 5 randomly selected rabbits in the experimental group and the 5 rabbits in the control group were treated with the same methods to obtain the histological samples.MAIN OUTCOME MEASURES: The symptoms and physical signs,contents of anti-Campylobacterjejuni antibody, anti-IgG GM1 antibody and MBP, imaging observation and histological examination were mainly observed.RESULTS: Fifteen animals were enrolled, 14 were involved in the analysis of results, 1 rabbit in the experimental group died at 4 weeks after immunization. ① Mental symptoms and disorder of limb's activity occurred in 1 rabbit in the experimental group at 2 weeks after immunization. ② In the experimental group, titre of anti-Campylobacterjejuni-IgG antibody in serum reach the peak at 2-4 weeks. From week 2, the serum A value was significantly higher in the experimental group than in the control group (1.923±0.403, 0.973±0.633, P ＜ 0.05). The IgG type GM1 (A value) was obviously elevated at week 8, but insignificantly different from that in the control group (0.115±0.042, 0.097±0.039, P ＞ 0.05). The MBP content (Avalue) in serum was significantly elevated at the 8th week (0.134±0.041).③ The imaging examination showed that abnormal MRI signal of different degree occurred at 2-4 weeks after immunization in the experimental group. ④ The histological changes showed that there was swelling of myelin sheath at the sites of brainstem, medulla oblongata, cervical spinal cord, thoracic spinal cord and lumbar spinal cord in the experimental group, no inflammatory cell infiltration and deletion of myelin sheath were observed. No obvious changes at the above site were observed in the contro1 group.CONCLUSION: Campylobacterjejuni Penner 4 can induce lesion of central nervous system.

BACKGROUND: Vascular endothelium growth factor (VEGF) is an endothelium mitogen and angiogenic factor with strong potential during recovery from cerebral infarction (CI). Can such therapeutic effect be detected with magnetic resonance diffusion imaging?OBJECTIVE: To study the therapeutic efficacy of VEGF plasmid in treating focal cerebral infarction in a dog experimental model with the aid of diffusion- and hemodynamic-weighted magnetic resonance imaging (MRI),with the morphological results compared with those of immunohistochemical examination.DESIGN: Completely randomized controlled, double blind evaluation,analysis of variance, Pearson correlation analysis, follow-up for 2 weeks.SETTING: Department of Medical Iconography, the Second Affiliated Hospital of Hebei Medical University.MATERIALS: This study was carried out at the Department of Medical Iconography, the Second Affiliated Hospital of Hebei Medical University,between April 2001 and March 2002. Totally 18 healthy adult dogs weighing 10-15 kg were randomly divided into control group and experiment group with half in each.METHODS: All dogs were subjected to femoral intubation and then made into CI model by the occlusion of middle cerebral artery with an embolus injected through the internal carotid artery. Dogs in control group were put to death at postoperative 24 hours, 1 week and 2 weeks with three at each time point, while four dogs in experiment group were put to death at postoperative 1 week and five at 2 weeks. Dogs in experiment group received microinjection of 0.5 mL fluid containing pcD2/hVEGF121 (500-600 μg)instantly after operation, which was replaced with physical saline of the same volume at the same time point in control group. Then they were subjected to MRI scanning once an hour for 4 times, with the sequence of T1WI, T2WI, 3D-TOFMRA, DWI and CET1WI, which was repeated at postoperative 24 hours, 3 days, 1 week and 2 weeks. Based on the MR images, pathological focuses were selected for morphological observation of cells with the aid of HE staining, and CD34 IHC staining was used for counting micrangium, as well as VEGF staining for VEGF positive cells.Then the apparent distribution coefficient (ADC) was calculated, and the differences between different time points and groups were analyzed by analysis of variance. The number of capillaries and VEGF positive cells of each high-power field was counted, with the results compared with those of MR scanning so as to explore the correlation between MR signal changes and IHC results.MAIN OUTCOME MEASURES: ① The number of capillaries and VEGF positive cells in each high-power field was counted at postoperative 24 hours, 1 week and 2 weeks; ② MR images of each group.RESULTS: Data of the 18 dogs entered the final analysis. ① Diffusionweighted imaging (DWI) showed higher signals at infarctional region at postoperative 1 hour, which became strengthened as time went by. ②ADC decreased to (5.61 ±1.39) mm2/s at postoperative 3-4 hours, about 43% lower than that of the opposite hemisphere [(9.85±2.04) mm2/s]. It resumed to (9.83±1.11) mm2/s, but was still lower than the normal level.③ The subsequent MR scanning proved that ADC ratio presented an increasing tendency in contrast with the decreasing tendency at super-acute stage. The increment was even more marked in control group and the difference was significant at postoperative 2 weeks (P=0.032, 0.006). ④ The number of capillary positive cells on the affected side in experiment group was significantly higher than that in control group at postoperative 2 weeks [(28.80±3.29)/field, (20.70±4.47)/field, (P ＜ 0.01)]. ⑤ The number of VEGF positive cells on the affected side in experiment group was significantly higher than that in control group at postoperative 1 and 2weeks [(64.20±9.40)/field, (51.90±5.74)/filed; (72.70±6.98)/filed,(58.40±6.35)/field, (P ＜ 0.01)].⑥ The results of MR scanning and IHC were subjected to correlation analysis and revealed that ADC ratio was closely correlated with the number of capillary positive cells, with Pearson correlation coefficient being 0.679 (P ＜ 0.01). Moreover, the number of capillaries and the number of VEGF positive cells were significantly correlated (r=0.668, P ＜ 0.01).CONCLUSION:Morphological observation and IHC revealed that both the local capillaries and VEGF protein content increased markedly in timedependant manner due to VEGF plasmid gene therapy.Meanwhile,the change of ADC ratio was found to be closely correlated with the number of VEGF positive cells and the number of capillaries.

To observe the morphology and anatomic variations of the circle of Willis and its clinical significance. To measure and establish the normal reference parameters of average diameters of its component vessels in the healthy Chinese by using 3D-TOF MR angiograms and to determine whether age-or sex-related differences exists in the circle' anatomy. MRA was performed in 153 healthy subjects. According to its integrity, Willis'circle was divided into four types: (1) Type I, showing an intact circle. (2) Type II, having a complete anterior circulation but an incomplete posterior circulation. (3) Type III, having an incomplete anterior circulation but a complete posterior circulation. (4) Type IV, having an incomplete anterior and posterior circulation. Based on the development of the components of the circle, each type was subdivided into four subtypes: typical, variable, hypoplastic and mixed. The statistically significant differences were not found in each type or subtypes between the different age and sex groups. Result of 153 cases, Type I, II, III and IV was found in 53 (34.64%), 73 (47.71%), 8 (5.23%), and 19 (12.42%) respectively. The display rate of the anterior and the posterior communicating arteries was 87.58%o (134/153) and 65.34% (100/153) respectively. Display rate of fetaltype posterior cerebral artery(PCA) was 20.92%. 3D-TOF MR angiography has important clinical significance for evaluating morphology and anatomic variations of circle of Willis. The normal values of diameter of cerebral arteries on MR angiograms may play a reference role in diagnosing cerebral vascular diseases.
Adolescent ; Adult ; Aged ; Anthropometry ; Child ; Child, Preschool ; Circle of Willis ; anatomy & histology ; diagnostic imaging ; Female ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Radiography

Objective To evaluate the differences in efficacy,safety and economics of vancomycin hydrochloride for injection between two manufacturers based on real-world data.Methods A total of 6 757 cases of intravenous use of vancomycin hydrochloride for injection from different manufacturers between January 1,2013 and December 31,2019 in the Affiliated Drum Tower Hospital of Nanjing University Medical School were retrospectively analyzed,and 5308 cases were matched by 1∶1 propensity score method,including 2 654 cases in the group A(domestic drug group)and 2 654 cases in group B(the innovator drug group).The differences in efficacy and safety between the two groups were compared.Cost-effectiveness analysis was used to compare the drug economics of the two groups.Results There were no significant differences in clinical cure rate,bacterial clearance rate,and incidence of adverse events between the two groups(P>0.05).In terms of economics,the average cost of vancomycin per capita,average daily cost of vancomycin and average cost of antibiotics per capita were significantly different between the two groups(P<0.05),and the cost of group B was higher than that of group A.Conclusion The efficacy and safety of vancomycin hydrochloride for injection were consistent between the two manufacturers.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.

Objective: First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients. Methods: Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2). Results: Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP. Conclusion Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.