Volume 89  ·   Issue 25  ·  2009

In recent years, the development and application of tumor targeted therapeutic drugs have received extensive attention. At present, the anti-tumor targeted drugs in clinical use generally include small molecule drugs and antibody drugs.

Atherosclerotic stenosis of intracranial aorta is one of the important causes of acute cerebral infarction and transient ischemic attack [1], and its incidence varies greatly according to different people [2].

Objective To study the differential gene expression of adriamycin-resistance of breast cancer cell line MCF-7/ADR as compared with its parent cell MCF-7 and screen the related genes. Methods The in vitro inhibitory rate of MCF-7/ ADR and MCF-7 cell lines to ADM (adriamycin) was examined by MTT assay. Then a cDNA microamay representing 14 755 genes was used to analyze the expression profiles of these two breast cancer cell lines. Results The inhibitory rate of MCF-7/ADR to ADM was lower than that of MCF-7 (P < 0. 05)and the drug resistance to ADR of MCF-7/ADR was stronger than that of MCF-7. There were 2374 differential expression genes in MCF-7/adr and MCF-7 cell lines, of which 1099 genes upregulated with 99 genes 10-fold upregulated and 1275 genes downregulated with 71 genes 10-fold downregulated. The important upregulated genes were Bcl-2, GSTP1, c-myc, MMP-1 and NNMT while those downregulated ones p53, p21, p27 and CYPIA1. Conclusion Drug resistance of breast cancer is a complicated process involving the expresison of many upregulated or downregulated genes. The application of gene chip in screening drug-resistant genes may be a new approach for selecting the optimal chemotherapeutic regimens.

Objective To investigate the drug resistance, proportion of leukemia stem cells (LSC) and expression of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-sensitive and multidrug-resistant leukemia cell population. Methods The multidrug-resistant leukemia K562/ADM cell and its parental K562 cell were used as the model cells. The drug sensitivity was tested with a MTI" assay. Flow cytometry was employed to detect the immunophenotype of stem celia and the expression of P-gp and BCRP. The serf-renewal and proliferating potential were examined with methylcellulose colony-formlng unit assay. Results K562/ADM cells were highly resistant to adriamycin, daunorubincin and etoposide. The amount of CD34+, CD123+ and CD34+ CD38- cells in K562/ADM cells was much higher than that in K562 cells, and the proportion of CD34+ CD38-CD123+ cells(LSC) in K562/ADM cells was (5.23 ± 0. 21) % versus (1.27 ± 0. 17) % in K562 cells, which was 4. 12-fold higher than that in K562 cells. Both P-gp and BCRP were overexpressed in K562/ADM cells relative to K562 cells, and the K562/ADM cells co-expressing P-gp and BCRP were 11.25-fold higher over K562 cells. The proportion of CD34+ CD38- CD123+BCRP+ and CD34+ CD38- P-gp+ BCRP+cells in K562/ADM cells were (4. 13±0.40)% and (5. 80 ± 1.19)% respectively, which were 3.66- and 11. 37-fold higher than the same cells in K562 cells [(1.13 ± 0. 15) % and (0. 51 ± 0. 01) %]. Furthermore, drug-resistant K562/ADM cells displayed 4. 17-time greater colony-forming ability over the parent K562 cells, corresponding to the proportion of LSCs in K562/ADM cells. Conclusions The ABC transporters-overexpressing LSC population exists in drug-resistant leukemic K562/ADM cells relative to drug-sensitive K562 cells, and the drug-resistant LSCs may be the source of chemotherapeutic resistance of leukemia.

Objective To evaluate the in vitro effects of lidamycin upon vasculogenic mimicry and apoptosis induction in glioma cells. Methods Tube formation assay was performed to estimate the inhibitory effects of lidamycin upon vasculogenic mimicry in C6 and U87 glioma cells. The vasculogenic mimicry of glioma cells was photographed and enumerated. Annexin V-FITC/PI was used for determination of glioma cell apoptosis with flow cytometry. Results Vasculogenic mimicry assay indicated that 0. 1 nmol/L, 0. 5 nmol/L and 1 nmol/L lidamycin showed significant inhibition of vasculogenic mimicry in C6 and U87 cells. Comparing with C6 control group (14. 7 ± 1.2), 0. 1 nmol/L (12. 7 ± 0. 6), 0. 5 nmol/L (9. 0 ± 1.7) and 1 nmol/L (4. 7 ± 0. 6) lidamycin inhibited vasculogenic mimicry in C6 cells with statistical significances (P = 0. 013, P = 0. 005 and P = 0. 0002 respectively). Comparing with U87 control group (14.7±1.2), the vasculogenic mimicry of 0.1 nmol/L (10.0±2.0), 0.5 nmol/L (8.3±1.5) and 1 nmol/L lidamycin (4. 3±0. 6) treated U87 cells showed statistical significances (P =0. 025, P =0. 005 and P =0. 0009 respectively). The apoptotic ratios of same dosages lidamycin treated C6 cells and U87 cells showed a similar tendency as vaaculogenic mimicry inhibition (P < 0. 001). Lidamycin was more potent than neocarzinostatin in vasculogenic mimicry inhibition and apoptosis induction of C6 cells and U87 cells. Conclusion Lidamycin can inhibit vasculogenic mimicry and promote apotosis of glioma cells. Thus it is a promising drug in glioma treatment. Further researches on the therapeutic efficacy of enediyne antibiotics in glioma are needed.

Objective Clinical and radiographic results in 30 consecutive patients undergoing posterior lumbar fixation and posterior facet joint or posterior interbody fusion for Meyerding Grade Ⅱ/Ⅲ spendylolisthesis were assessed: (1) to address the suitability of a dynamic stabilization; and (2) to investigate whether there are differences in terms of clinical and functional results between these two types of arthrodesis. Methods Fourteen patients underwent posterior inteffacet fusion (PLF) and implantation of TSRH-3D system. Posterior lumbar interbody fusion (PLIF) and placement of the same system were performed in 16 patients. Clinical, economic, functional and radiographic data were recorded both pre- and postoperatively. Results The average changes in Prolo Scale of economic and functional scores were 1.25 and 1.64 respectively, in patients undergoing posterior fusion; the average measured vertebral slippage was 48.6% (range 32% -65%) preoperatively and 17. 5% (range 15% -25%) postoperatively. In patients undergoing PLIF, the average changes in economic and functional score were 1.18 and 1.39 respectively, and the average preoperative vertebral slippage was 44. 2% (range 30% - 55%) versus 20. 3% (range 18% -26%) postoperatively. Conclusion The use of a segmental pedicle screw fixation with TSRH-3D was able to successfully combine the goal of solid fusion with the requirements of nerve root decompression. When these two fusion techniques were compared, PLIF was superior to PLF because of an overall superior reliability and system resistance. But their clinical outcomes did not differ greatly (P > 0. 05).

Objective To present some instruction in diagnosis and treatment of the orbital fistula by analyze the clinical manifestation. Method The clinical data for 37 cases with orbital fistula treated during 1980 to 2007 were analyzed retrospectively. Results Among 37 cases with orbital fistula, there are 21 cases caused by foreign bodies, including 17 cases by retained wooden bodies, 3 cases by iatrogenic foreign bodies and 1 case by firecrackers. There are 9 cases caused by orbital cysts, including 5 cases dermoid cysts, 3 cases epidermoid cysts and 1 case frontal mucopyocele. There are 6 eases orbital infection inflammation, including 5 cases osteomyelitis and 1 case orbital abscess. There is 1 case eosinophilic granuloma. Different etiologies have characteristic features. Medical history, fistula examinations and imaging examinations must be analyzed synthetically in order to make proper etiological diagnosis. Eradicate etiologies and resect fistula are most important. It is necessary to make an ancillary therapy, sueh as ENT treatment. Conclusions The common etiologies of orbital fistula are retained foreign body, dermoid cysts and osteomyelitis. The pathogenesy include infective inflammation, congenital hetereplasia, operation and tumor. B-scan ultrasonography, CT, and MRI can be used for the localization and qualitation diagnosis. There are comprehensive approaches for diagnosis and management of this type of injury. In order to give an effective therapy, we must make an accurate diagnosis and analyze the features of fistula.

Objective To determine the postoperative survival of non-small cell lung cancer with peripheral adjacent lobe invasion by comparing it with that of resectable T4 disease with mediastinal structures invasion, and hence try to find out some clue concerning how to define these patients for a reasonable T stage. Methods A retrospective analysis was conducted to assess the survival of NSCLC patients with peripheral direct adjacent lobe invasion (group A, n = 28), and compared it with that of with mediastinal structures invasion (group B, n =21). All patients underwent surgery between March, 1997 and October, 2006, and were pathologically confirmed with NOMO disease. Kaplan-Meier method was used to calculate the survival, and Log-Rank test was used to compare the postoperative survival between two groups. Results The sex, age, pathology, and pulmonary function were well balanced between the two groups. There was one operative death from group A. The disease specific 2 year, 3year, 5 year survival in group A and group B was: 68.7%, 61.1%, 40. 7%, and 64. 7%, 58.2%, 43.7%, respectively. The median survival for group A and group B was 54 months and 49 moths, respectively, with no statistically significant difference (P =0. 931). Conclusions NSCLC with peripheral adjacent lobe invasion has a similar survival prognosis with that of resectable T4 disease with mediastinal structures invasion. Among carefully selected patients, long-term survival is anticipated for NSCLC with adjacent lobe invasion. However, further studies are needed to determine the optimal T stage for these patients.

Objective To evaluate the ability of the RIFLE classification to predict hospital mortality in adult patients who underwent cardiac surgery. Methods From October Ist 2006 to December 31st 2006, five hundred and nine adult patients who underwent coronary artery bypass grafting and/or valve operation were enrolled in this study. Renal function was assessed daily according to the RIFLE classification, meanwhile, APACHE Ⅱ score and SOFA score were also evaluated, as well as the maximum scores were recorded. Results Mean duration of ventilation support was 18(14 - 19) hours, the time of ICU stay was 1.4 ± 1.0 days, and the time of postoperative hospital stay was 12. 0(10.0- 15.0) days. 167 patients (32. 8%) incurred postoperative ARF according to the RIFLE classification. The overall mortality was 4. 3% (22/502). A significant increase (P < 0. 01) was observed for mortality based on RIFLE classification. By applying the area under the receiver operating characteristic curve, the RIFLE classification had more powerful discrimination power [0. 933, (95% CI 0. 872 -0. 995) ,P <0. 001]. Conclusions ARF is one of the major complications in postcardiotomy patients. Analytical data suggested the good discriminative power of the RIFLE classification for predicting inpatient mortality of adult postoperative patient with ARF, and the RIFLE classification is simple and practically performed. According to the RIFLE classification, patients with RIFLE class I or class F incur a significantly increased risk of in-hospital mortality compared with those who never develop ARF.

Objective The ann of trial is to observe the Chinese bleeding frequency and frequency of recurrent VTE in different international normalized ratio (INR) range of warfarin for venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE) ,and to search optimal INR range. Methods We conducted a randomized, double-blind cohort trial, in which 180 patients were assigned to apply warfarin in a target INR of 1.50 to 1.99 (group A), a target INR of 2. 00 to 2. 50(group B) or a target of INR of 2. 51 to 3.00 (group C). Every group had respectively 60 patients. After they had completed warfarin therapy to be stabilely kept with those target INR range for two or more weeks, this study would be begun to observe the bleeding frequency and frequency of recurrent VTE. Results There was significant difference in recurrent VTE frequency between Group A (8. 3%) and BC (1.7%, P=O. 042). The minor bleeding frequency of Group A, B and C is respectively 8.3%, 18. 3% and 6. 7% (P = 0. 089). The moderate bleeding frequency of Group A and BC is respectively 3. 3% and 7.5% (P =0. 341), and large bleeding frequency of them is respectively 0% and 3. 3% (P = 0. 303). To patients whose age above 62 year, major bleeding episode occurred respectively in I patient assigned to INR of 1.5- 2.5 and in three patients assigned to Group C (bazard ratio, 12.600; 95 percent confidence interval, 1.183-134.238). Conclusion Warfarin therapy in INR of 2. 0 - 3. 0 is more effective than INR of 1.5 - 1.99 for the long-term prevention of recurrent VTE. And warfarin regimen in INR of 2. 0 - 3.0 does not increase the risk of major bleeding either. So to general Chinese, INR ought to be reccmended in 2. 0 -3.0. To patients whose age above 62 year, INR ought to be recommended between 2. 0 to 2. 5.

Objective To evaluate the clinical practical value of apparent diffusion coefficient (ADC) measurements based on diffusion-weighted MR imaging (DWI) for quantification of liver fibrosis and inflammation for hepatitis viral infection.Methods Diffusion-weighted MRI with parallel imaging was prospectively performed on 85 patients with chronic hepatitis and on 22 healthy volunteers within a single breath-hold using a single-shot spin-echo echo-planar sequence at b values of 100, 300, 500,800 and 1000 s/mm2 respectively. ADC values of liver were measured with five different b values. The inflammation grades and fibrosis stages were evaluated histologically by biopsy. One-way analysis of variance and Spearman' s rank correlation test were used for statistical analysis. Receiver operating characteristics analysis was used to assess the performance of ADC in predicting the presence of stage ≥2 and stage ≥3 hepatic fibrosis, and grade ≥1 hepatic inflammation. Results There was moderate negative correlation between hepatic ADC values and fibrosis stage. And the best correlation was obtained for a b value of 800 s/mm2 (r = - 0. 697, P=0.000). At all b values there was a significant decrease in hepatic ADC in patients with stage ≤1versus stage ≥2 fibrosis and stage ≤2 versus stage ≥3 fibrosis (P <0. 05). Hepatic ADC was a significant predictor of stage ≥2 and ≥3 fibrosis. The areas under the curve were 0. 909 vs 0. 917, sensitivity 76. 6% vs 80. 0% and specificity 88. 3% vs 91.5% (ADC with a b value of 800 s/mm2, 1.26 × 10<'3> mm2/s or less and 1.19 × 10-3 mm2/s or less). There was weak to moderate negative correlation between ADCs and inflammation grade. Hepatic ADC was a significant predictor of grade ≥1 inflammation with an area under the curve of 0. 781, sensitivity of 60. 0% and specificity of 86. 4% (ADC with a b value of 500 s/mm2, 1.54 × 10-3 mm2/s or less). Conclusion The D WI measurement of hepatic ADC can be used to quantify liver fibrosis and inflammation. It will be a new approach for early diagnosis and therapeutic follow-up of hepatic fibrosis.

Objective To analyze the pathogenic mutation of sporadic patients in Duchenne/ Becker muscular dystrophy (DMD/BMD) families and to perform prenatal diagnosis, identify the female carders and evaluate the ratio of de novo mutation in these pedigrees. Methods A total of 30 sporadic DMD/BMD families were included. Traditional multiplex PCR was used to detect the 18 exons in the deletion hot area of DMD gene. MLPA was used to detect the deletion or duplication mutations of DMD gene for 30 patients and 28 females from 23 families. Prenatal diagnosis was performed in 19 families. Results Deletion mutation was detected in 19 patients through mPCR. Twenty-one deletions and 3 duplication mutations were detected by MLPA. Among 21 mothers, 10 mothers were carriers of deletion mutation and two duplication mutation carriers. The other 9 mothers were non-carriers, the mutations in these families were de novo and the ratio was 37.5%. Among seven sisters, five were arriers and two non-carriers. In the prenatal diagnosis families, 2 of 8 female fetuses were carriers and 5 of 12 male fetus patients. Conclusion The MLPA technique has proved to be an accurate and reliable tool not only for the deletion and duplication mutations of DMD patients, but also for the prenatal diagnosis and the female carriers in these families.

Objective To determine the prevalence and risk factors of diabetic retinopathy (DR) in the Diabetes Mellitus (DM) and impaired glucose regulation (IGR) population in Shanghai Community. Methods DR screening after the epidemiologic study of metabolic syndrome in Huayang and Canyang Community , Shanghai was conducted among 1300 patients with DM or IGR during June 2005 and March 2006, Digital non-mydriatic fundus photography was performed for each eye in all subjects. Other factors, including diabetes related history, BMI, WHR, fasting plasma glucose, HbAlc, serum lipid and blood pressure were also assessed. 642 patients,312 males and 330 females, aged 65 ± 13, with complete data were enrolled into the analysis. Results The prevalence of DR was 19. 9% in the diabetic population, and the prevalence of mild, moderate, severe non-proliferative retinopathy and proliferative retinopathy was 12. 0%, 5. 1%, 2. 3% and 0. 5%, respectively; the prevalence of DR in IGR reached 8. 0%. Logistic regression analysis revealed that HbA1c level and diabetes duration were both independently associated with diabetic retinopathy. Conclusion The prevalence of DR was high in both DM and IGR population. Bad blood glucose control and long diabetes duration both increased occurrence of DR.

Objective To detect the expression and distribution of M4 receptor in normal guinea pigs retina. Methods Twenty one normal 4-week-old triad color guinens were selected. Eyes were enucleated. Seven eyes were fixed, paraffin-embeded and cut into sections. Expression and distribution of M4 receptor were detected using immunohisto chemically. The rest eyes were dissected. Tissue of retina were separated. RNA and protein of different tissue were extracted respectively. M4 receptor at mRNA level and protein level were detected by RT-PCR and Western blot methods. Results receptor at mRNA level was detected in normal guineas retina, with the amplification product at 221 bp. No product was detected in negative control. M4 receptor at protein level was detected in normal guineas retina, with signal band at 38 000. No signal was detect in negative control. As detected by immunohistochemistry, M4 receptor was detected in RPE cells, photoreceptor layer, outer nuclear layer, inner nuclear layer, most ganglion cells and the junctional zone of inner plexiform layer and inner nuclear layer. Conclusion M4 receptor was expressed in normal guineas retina.

Objective To investigate the effects of [ntralipid injection on hemodynamics and pharmacodynamics of mongrel dogs with bupivacaine-induced cardiac depression. Methods Fourteen dogs were randomly divided into Intralipid injection group (the experiment group) and normal saline group(the control group). 0. 5% bupivacaine was administrated at a constant rate until the mean arterial pressure (MAP) decreased to 60% of the basic value. Intralipid injection was administered in the experiment group. The hemedynamic parameters were recorded and blood samples were taken from femoral artery at 0, 5, 10, 15, 20, 30, 45,60, 90,120, 180,240 min after stopping bupivacaine infusion for determination of plasma concentration by HPLC. The pharmacokinetic parameters were calculated by Drug and Statistics soft version 2. O. Results After the treatment of Intralipid injection, MAP, CO, HR increased significantly, compared min-1 in the experiment group and the control group respectively. Vz (4. 5 ± 1.1 L/kg versus 3. 3 ± 0. 9 L/kg)of bupivacaine in the experiment group was significantly higher than that in the control group(P < 0. 05). Conclusion Intravenous infusion of Intralipid have beneficial effects on the hemodynamics of mongrel dogs with bupivaeaine-induced cardiac depression. One of the mechanism of the beneficial effects was probably that Intralipid injection increases the apparent volume of bupivacaine distribution and that decreases blood concentration.

Objective To evaluate the inhibitory effects of VCAM-1 siRNA on VCAM-1 protein expression and restenosis following carotid endarterectomy in rats. Methods Lentivirus-based VCAM-1 siRNA was constructed and its efficacy of blocking VCAM-1 protein expression in endothelial cells and carotids was identified by Western blot. Doppler ultrasonography and morphometric analysis were performed to measure the degree of restenosis. Results VCAM-1 siRNA decreased the protein expression of VCAM-1 in cultured endothelial cells and carotids. Treatment of VCAM-I siRNA showed a significant reduction in the restenosis and manifested as an increased blood velocity and linear diameter as compared with control siRNA (P < 0. 05) . Morphometric analysis showed that the ratio of intima to media area (I/M) increased significantly in CEA group (3.99 ± 0. 65) versus sham-operated group (0. 35 ± 0. 13) (P < 0. 05). Furthermore, VCAM-1 siRNA resulted in an evident decrease in the neointimal area (1.79 ± 0. 43) as compared with that of the control siRNA (4. 33 ± 0. 59) (P < 0. 05). Conclusion VCAM-1 plays an important role in pathogenesis of restenosis after carotid endarterectomy. VCAM-1 siRNA blocks VCAM-1 protein expression and alleviates the restenosis following carotid endarterectomy in rats.

Enzastatmin (LY317615) is a potent oral inhibitor that acts selectively on silk/threonine protein kinase. Because it competes with β-type protein kinase C for adenosine triphosphate, it was initially developed as an anti-angiogenic PKC β (β isomer of protein kinase C isoform) inhibitor

For a long time, intraspinal block anesthesia has become the main anesthesia method in China because of its economy and applicability. The number of cases and the wide range of applications are the first in the world. It is of wide practical significance to standardize its clinical practice and reduce the occurrence of complications in China.

Confirmed cases of influenza A (H1N1) can be discharged when the following conditions are met at the same time: 1. The body temperature is normal, the influenza-like symptoms disappear for ≥3 days, there are no complications, and the clinical condition is stable;

In order to effectively deal with the epidemic of influenza A (H1N1), prevent the infection of related personnel among close contacts as much as possible, and delay and reduce the secondary cases, refer to the CDC of the United States<Interim Guidance on Antiviral Treatment in Patients with Influenza A (H1N1) and Close Contacts (May 6, 2009 Edition)>and the World Health Organization<Guidelines for the Application of Vaccines and Antiviral Drugs during Influenza Pandemic (2004 Edition)>, combined with China's preliminary experience in the prevention and treatment of influenza A (H1N1), this paper studies and formulates this guideline.

A 14-year-old female, weighing 40 kg, was admitted to hospital because she was found to have cleft palate for 14 years. She was diagnosed as congenital bilateral incomplete cleft lip and second degree cleft palate, and was planned to undergo cleft lip and palate repair.