Effects of Elemene Injection on the kinetics of intracellular transport of Gefitinib in PC-9/GR cells / 中成药

AIM To study the effects of Elemene Injection (ELE) on the kinetics of intracellular transport of Gefitinib (GEF) in PC-9/GR cells and to probe the role of ELE in reversing oncological multidrug resistance.METHODS The intracellular pharmacokinetic behavior of D-luciferin potassium salt,a substrate of an ATP-binding cassette (ABC) protein,was investigated in PC-9/GRFluc cells using real-time bioluminescence imaging.The resistance of PC-9/GR cells to GEF was determined by MTT assay.Compusyn software was used to analyze the synergistic effect of GEF and ELE,and HPLC to detect the uptake of GEF in PC-9/GR cells.RESULTS The respective GEF IC50 values of 0.01 μg/mL in PC-9 cells and 1.50 μg/mL in PC-9/GR cells revealed the 150 times drug resistance of PC-9/GR to PC-9 cells.The significantly enhanced intracellular fluorescence intensity of D-fluorescein potassium salt by the intervention of ELE also indicated remarkable GEF uptake increase in PC-9/GR cell line (P ＜ 0.05) due to the synergistic result.CONCLUSION Partly as the mechanism in reversing oncological multidrug resistance,ELE,a booster for the fluorescence intensity of D-luciferin potassium salt,promotes cellular uptake of GEF by inhibiting efflux function of ABC proteins.

Impact of Coix seed oil on fluorescence excretion pharmacokinetics and protein expression in doxorubicin-resistant cells MCF-7/DOX / 药学学报

This study was designed to explore the mechanism of Coix seed oil (Coix) impact on the drug resistance, bioluminescence imaging (BLI) and the efflux of D-luciferin potassium salt, the substrate of ABC transporters, in doxorubicin-resistant breast cancer cells. Multidrug resistance (MDR) gene and protein expression were analyzed in the cells by q-PCR and Western blot. First, in order to investigate the effect of the efflux function by ABC protein, a cell line with overexpressed luciferase was established in MCF-7 cell line. BLI was used to monitor the efflux kinetics of D-luciferin potassium salt before and after Coix treament. The results showed that the efflux of D-fluorescein potassium from MCF-7/DOXFluc was lessened when pretreated with Coix, which means that Coix may decrease the efflux of other chemotherapies using ABC transporters. Both of the results of q-PCR and Western blot showed that gene and protein expression of ABC transporters such as ABCG2, ABCC1 and ABCB1 were down-regulated by Coix treatment. The efficacy of Coix reversing MDR was verified with the chemotherapy medication doxorubicin (DOX). MTT assay showed that Coix increased the inhibitory effect of DOX on proliferation of MCF-7/DOX, and the optimal combination of ratio was 25 times that of DOX. The results suggest that Coix may reverse MDR of the substrate of ABC transporters from two aspects, one is to cut down the ABC protein efflux function, and the other is to decrease the quantity of ABC gene and protein expression.

Correlation of in vitro release between total flavonoids and different ingredients in sustained-release pellets of Ginkgo biloba extract by f2 fit factor method / 中草药

Objective: To find a new method to evaluate the in vitro release of Ginkgo biloba extract (GBE) sustained-release pellets, f2 fit factor method was used to study the correlation of in vitro release between total flavonoids and different ingredients (including flavonoids and terpenoids). Methods: The release rates in vitro of total flavonoids and different ingredients (quercitrin, isorhamnetin, lutin, quercetin, ginkgolide A, ginkgolide B, ginkgolide C, and bilobalide) were detected by UV and HPLC-MS respectively, and then f2 fit factor was calculated between total flavonoids and different ingredients. Also the micro-structures of pellets before and after drug release were detected by scanning electron microscopy (SEM), which could explain the drug release mechanism combined with the fitted equation. Results: All f2 values were greater than 50 between the total flavonoids and different ingredients of the in vitro release from GBE pellets of optimized preparation, which indicated that there might be a good correlation between them. The drug release mechanism further verified the reliability of the results. Conclusion: The f2 fit factor method could be applied in the evaluation of in vitro release for multi-component sustained-release preparations of Chinese materica medicine.

Expression and clinical significance of caudal type homeobox transcription factor-2 in adult acute lymphocytic leukemia / 中国实验血液学杂志

This study was aimed to investigate the expression and clinical significance of CDX1, CDX2 and CDX4 genes in acute lymphocytic leukemia (ALL). Expressions of CDX1, CDX2, and CDX4 in 51 adult acute lymphocytic leukemia patients and 14 healthy subjects were detected by reverse transcription polymerase chain reaction (RT-PCR). The results indicated that CDX1, CDX2 and CDX4 were not expressed in 14 healthy persons and 15 CR ALL patients, the positive expression rate of CDX2 gene in de novo ALL patients was 60.8%, while it obviously decreased in patients with complete remission (CR) (p < 0.05); the expression of CDX2 was increased again in relapsed patients (81.8%). When the expression of CDX2 was analyzed in different risk groups of ALL patients, the CDX2 expression rate in high risk (HR) patients was 91.7%, and that in the standard risk (SR) group was 45.7%. Furthermore, analyses of CDX1 and CDX4 expression in series of ALL samples did not show the expression of these genes. In patients with adult ALL at diagnosis and relapse, the CR rate of patients with CDX2 positive expression was lower than that of patients with CDX2 negative expression (p < 0.05). The median survival time in CDX2 positive expression patients was shorter than that in negative expression patient. It is concluded that expression of CDX2 may correlated with pathogenesis and relapse of adult ALL, but the expression of CDX1 and CDX4 don' t associated with pathogenesis and relapse of adult ALL; the CR rate and prognosis of patients with CDX2 positive expression is lower and poor. The expression of CDX2 may be used as a marker for occurrence, relapse and poor prognosis of adult ALL patients.

Pullout test in expansive unilateral open-door laminoplasty of the cervical spine with OsteoMed M3 plate and screws: the screw orientation matters / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the impact of screw orientation on the pullout strength of OsteoMed M3 titanium screws in expansive unilateral open-door laminoplasty of the cervical spine.</p><p><b>METHODS</b>Six fresh human cervical spine specimens were randomly numbered and OsteoMed M3 plate and screws were used for an expansive unilateral open-door laminoplasty. The screws were inserted in the lateral mass at different extraversion angles (0°, 30° and 45°). The maximum pullout strength was tested on the ElectroForce material testing machine.</p><p><b>RESULTS</b>The maximum pullout strength was 81.60∓7.33 N, 150.05∓15.57 N, and 160.08∓17.77 N in extraversion angle 0°, 30°, and 45° groups, respectively. The maximum pullout strength was significantly less in extraversion angle 0° group than in 30° and 45° groups (P<0.05), but similar in the latter two groups.</p><p><b>CONCLUSION</b>The pullout strength of the screws inserted at an extraversion angle over 30° provides stronger fixation than an angle of 0° in the unilateral open-door laminoplasty using OsteoMed M3 titanium plate and screws.</p>

Percutaneous radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta analysis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the curative effect of percutaneous radiofrequency ablation (RFA) and hepatic resection (RES) for small hepatocarcinoma eligible for Milan criterion using meta analysis method.</p><p><b>METHODS</b>Retrieved clinical trials comparing percutaneous radiofrequency ablation with RES for small hepatocarcinoma published from 1990 to 2010. A meta-analysis was conducted to estimate overall survival and disease free survival. A fixed random effect model or random effect model was established to collect the data.</p><p><b>RESULTS</b>Four randomized controlled trials were included in this analysis. These studies included a total of 539 patients: 252 treated with percutaneous RFA and 287 treated with RES. The differences in overall survival were not statistically significant between RFA and RES (P > 0.05). In the patients treated with RES group, the 2-, 3- and 4-years disease free survival rates were significantly better than that in the patients treated with percutaneous RFA (P < 0.05). The postoperative morbidity rate was significant lower in patients treated with percutaneous RFA (OR: 0.14, 95%CI: 0.09 - 0.22, P = 0.000). But percutaneous RFA had a higher rate of tumor recurrence compared to RES (OR: 2.63, 95%CI: 1.67 - 4.15, P = 0.000).</p><p><b>CONCLUSIONS</b>For small hepatocarcinoma eligible for Milan criterion, percutaneous RFA had a similar overall survival to RES. Percutaneous RFA was the invasive lesser and had a lower postoperative morbidity rate than RES, but RES may had a better prevention of the tumor recurrence than percutaneous RFA. For those patients who don't want to be treated by RES, percutaneous RFA may be a recommendable choice.</p>

Indication of fusion for degenerative lumbar spinal stenosis treated by "windows technique" laminoforaminotomy / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the indications of fusion for degenerative lumbar spinal stenosis treated by "windows technique".</p><p><b>METHODS</b>From December 1999 to December 2005, 145 consecutive patients who were treated by primary decompression with "windows technique" laminoforaminotomy for degenerative lumbar spinal stenosis, a retrospective study, were divided into 3 groups (A and B and C) by preoperative lumbar conditions and surgical methods. In group A, 39 patients with spinal instability or degenerative lumbar spondylolisthesis or scoliosis underwent decompression and fusion; in group B, 31 patients with spinal instability or degenerative lumbar spondylolisthesis or scoliosis underwent decompression alone; In group C, 75 patients without spinal instability or degenerative lumbar spondylolisthesis or scoliosis were treated by decompression without fusion. On hospital medical records to review, they were followed up by telephone and out-patient referral. Statistics the duration of hospitalization, operative time, estimated blood loss; Observed recrudescence and reoperation and complication; and using Oswestry Disability Index and Visual Analog Scale and satisfaction rate for efficacy assessment, application SPSS 13.0 software.</p><p><b>RESULTS</b>All 145 patients had at least a 3-year follow-up (ranging 37 to 108 months). In the group C, the duration of hospitalization less than in the group A or B (P < 0.05); In the group A, the operative time and estimated blood loss greater than in the group B or C (P < 0.05); The group B treated by decompression alone in the presence of instability or spondylolisthesis or scoliosis showed the worst results by the Oswestry Disability Index or Visual Analog Scale or ate of satisfaction (P < 0.05). The same good results can be obtained in the group A and C. There were not different about recrudescence or reoperation or complication in the three groups.</p><p><b>CONCLUSIONS</b>Fusion should be performed on patients with instability or degenerative lumbar spondylolisthesis or scoliosis after primary decompression with "windows technique" laminoforaminotomy. The patient with simple lumbar spinal stenosis undergone primary surgery does not require fusion.</p>

The value of hepatic ischemic preconditioning in hepatectomy with a prospective randomized controlled study / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of ischemic preconditioning in clinical hepatectomy.</p><p><b>METHODS</b>A total of 48 unselected patients undergoing liver resection were analyzed by randomized controlled trial from December 2004 to June 2006. Forty-eight unselected patients were randomized into two groups: IP group (5 minutes of ischemia followed by 5 minutes of reperfusion) and control group (received Pringle's maneuver no and no IP was given). Postoperative days 1, 3 and 7, the liver function were checked. Perioperative mortality, morbidity and hospitalized days were compared.</p><p><b>RESULTS</b>In IP group, ischemic times were 5 - 80 min, mean 31 min, hospitalized days were 13 - 50 days, mean 20 days. In control group, ischemic times were 10 - 60 min, mean 27 min, hospitalized days were 10 - 33 days, mean 17 days. Forty-seven patients were satisfactory with postoperative recovery, except one patient died of chronic liver dysfunction after 3 months postoperatively. Postoperative days 1, 3 and 7, the ALT, AST, TBIL, ALB levels in two groups were not statistically significant (P > 0.05).</p><p><b>CONCLUSIONS</b>The clinical use of IP through 5 minutes of warm ischemia in this technique of hepatectomy does not protect the liver from hepatic injury induced by the IRI.</p>

Ultrastructure study on patients with spontaneous rupture of hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the ultrastructure of small artery wall in patients with spontaneous rupture of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Transmission electron microscopy was used to study 11 specimens from ruptured HCC and 11 cases with non-ruptured HCC.</p><p><b>RESULTS</b>The phenomenon of activated phagocytosis in macrophage could be found in 3 cases with ruptured HCC and 10 cases with non-ruptured HCC, respectively (P < 0.05). In 9 specimens with ruptured HCC, the evidence of vascular injury characterized as less cell junctions and larger fenestrae in endothelial cells, broken elastic lamina, proliferated and fragmented elastin and damaged structure of collagen was found in small arteries. The phenomenon of electron-dense deposit in the elastic lamina, and signs of more protein synthesis in endothelial cells were also present in these specimens. In the patients with non-ruptured HCC, the evidence of vascular injury can be found only in 2 cases (P < 0.01). Less cell junctions and larger fenestrae could increase the permeability of vascular wall. The electron-dense deposition in elastic lamina may represent the deposition of antigen-antibody complex in elastic membrane which had been found in our previous study. The vascular injury was postulated to be caused by the deposition of antigen-antibody complex in vascular wall which was identified by our previous study. The vascular wall in the patient with ruptured HCC could become stiff and weak due to the proliferated fragment elastin and damaged collagen which would make the blood vessels more prone to splitting and result in hemorrhage and the rupture of HCC.</p><p><b>CONCLUSIONS</b>The vascular injury caused by antigen-antibody complex deposition might related to the spontaneous rupture of HCC.</p>

Clinicopathological significance of aberrant methylation of the fragile histidine triad gene in patients with hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the aberrant methylation of fragile histidine triad (FHIT) gene and to explore possible relationship between the aberrant methylation of FHIT and clinicopathological features in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The hypermethylation of FHIT was detected by the methylation specific PCR (MSP) method in 45 patients with HCC (tumoral and nontumoral tissue), 14 cases of normal livers and 4 HCC cell lines (SK-Hep-1, Hep-G2, Hep-3B and Huh7). The correlation of FHIT methylation and clinicopathological features was analyzed.</p><p><b>RESULTS</b>The frequencies of hypermethylation of FHIT in tumoral and nontumoral tissue, normal liver and cell lines were 71.1%, 64.4%, 14.3% and 75.0%, respectively. A significant relation between hypermethylation of FHIT and poor survival was present (P = 0.0430).</p><p><b>CONCLUSIONS</b>Hypermethylation of FHIT is a frequent and early event in HCC, it might relate to a poor prognosis for patients with HCC.</p>

Twenty four cases of cholesterol granuloma of the paranasal sinuses / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the etiology and pathogenesis of cholesterol granuloma of the paranasal sinuses and the treatment for the disease.</p><p><b>METHODS</b>Twenty four cases of cholesterol granuloma of the paranasal sinuses treated in our hospital during the period from March 1996 to March 2003 were retrospectively analysed. All cases were verified by surgery and pathology.</p><p><b>RESULTS</b>Of all cases, 10 cases were diagnosed as chronic sinusitis, 8 cases as nasal sinus cyst, and 5 cases as nasal polyp before operation, only 1 case was considered as cholesterol granuloma. The main symptoms were nasal obstruction (20/24), rhinorrhea (18/24), dysosmia (10/24), headache (7/24), pain around the eye (5/24), double vision (2/24), et al. Different surgical approaches were selected depending upon different pathological changes. Good results were obtained in 23 cases and postoperative follow-up for at least one year showed no recurrence. Only one case received revision nasal endoscopic surgery two years after Caldwell-Luc operation because of recurrence, and remained symptom-free for three years.</p><p><b>CONCLUSIONS</b>The pathogenesis of cholesterol granuloma includes obstruction of ventilation and drainage and brooding in sinuses. Cholesterol granuloma of the paranasal sinuses seems to have a close relation with chronic sinusitis, especially sinus mucocele. The surgical approach depends upon the location, extension, and severity of the lesion. The principle of surgery is to eliminate the pathological focus and create an adequate drainage.</p>

Hypermethylation of Ras association domain family protein 1A, hypermethylated in cancer 1 and p73 genes in hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the status of promoter hypermethylation of Ras association domain family protein 1A (RASSF1A), hypermethylated in cancer 1 (HIC1) and p73 genes in hepatocellular carcinoma (HCC) and to explore the correlation with clinicopathological features.</p><p><b>METHODS</b>Forty cases of HCC and their corresponding non-tumor liver tissues, other 2 cases of healthy donor livers were detected using methylation specific polymorphism chain reaction (MSP) method.</p><p><b>RESULTS</b>The frequency of promoter hypermethylation of RASSF1A showed 90.0% and 72.5% in tumor and corresponding non-tumor tissues respectively, and there was significant difference between them (P < 0.05). The frequency of promoter hypermethylation of HIC1 showed 77.5% and 70.0% in tumor and corresponding non-tumor tissues respectively. The frequency of hypermethylation of HIC1 in non-tumor liver tissues showed significant correlation between younger and older patients. The frequency of promoter hypermethylation of p73 showed 5.0% in tumor tissues. However, none of hypermethylation of the gene was detected in corresponding non-tumor liver tissues. There was none of hypermethylation of the three genes showed in two cases of healthy donor livers.</p><p><b>CONCLUSION</b>Promoter hypermethylation of RASSF1A and HIC1 genes are common event in HCC and play an important role in the pathogenesis and may be used to develop novel diagnostic and therapeutic approaches for HCC in the future.</p>

Mechanism of spontaneous rupture of hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To study the mechanism of spontaneous rupture of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The specimens of 30 patients with ruptured HCC and 30 patients with non-ruptured HCC were collected. Immunofluorescence, immunohistochemical and flow cytometry techniques were used to detect the phagocytosis of macrophages and the deposition of immune complex (IC) on vascular wall.</p><p><b>RESULTS</b>In this study, the poor function of macrophage phagocytosis was found in patients with ruptured HCC, which could results in the cumulating of IC and deposition on vascular wall. The IC, which composed of hepatitis B virus e1 antigen (HBeAg/1), complement C1q and immunoglobulins, was found deposited in the elastic membrane of arteries. Likely as a result of IC deposition, vascular injury occurs mainly in the small arteries where the deposition of IC was present. As the small arteries were the blood vessels with predominant injury, they would likely to be the ones to split and cause hemorrhage and rupture of HCC during vascular load increase.</p><p><b>CONCLUSIONS</b>We would conclude that the poor function of macrophage phagocytosis, which lead to the IC deposition and vascular injury may be the factors involved in the pathogenesis of ruptured HCC.</p>

Mechanism of Spontaneous Rupture of Hepatocellular Carcinoma / 中国普外基础与临床杂志

Objective To study the mechanism of spontaneous rupture of hepatocellular carcinoma(HCC).Methods Articles have been reviewed to find out the theory of spontaneous rupture of HCC.Results Researchful results suggested that the injury of small arteries was usually followed in patients of spontaneous rupture of HCC.In this review,the immune complex,which composed of hepatitis B virus e antigen,complement C1q and immunoglobulins,was found deposited in the elastic membrane of arteries.Likely as a result of immune complex deposition,vascular injury occurs mainly in the small arteries where the deposition of immune complex was present.The small arteries in which immune complex deposited are readily injuried and cause hemorrhage and rupture of HCC during vascular load increase. Conclusion We would conclude that immune complex deposition in vessel wall led to the small arteries injury may be the factor involved in the pathogenesis of spontaneous ruptured HCC.